Biochemistry, Genetics and Molecular Biology › Molecular Biology

Chemical Synthesis and Analysis

Works Count: 134984

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Description

This cluster of papers focuses on peptide synthesis, foldamers, amide bond formation, protein-protein interactions, diversity-oriented synthesis, and macrocycles in the context of drug discovery. It explores strategies for the design, synthesis, and application of peptides as therapeutic agents, as well as the development of novel methods for solid-phase peptide synthesis and chemical ligation.

Keywords

Peptide Synthesis; Drug Discovery; Foldamers; Amide Bond Formation; Protein-Protein Interactions; Diversity-Oriented Synthesis; Macrocycles; Chemical Ligation; Therapeutic Peptides; Solid-Phase Synthesis

Fmoc solid phase peptide synthesis : a practical approach

2000-01-01

Weng C. Chan , Peter D. White

Introduction - a retrospective viewpoint White & Chan: Basic Principles Chan & White: Basic Procedures Albericio et al: Preparation and Handling of Peptides Containing Methionine and Cysteine Quibell & Johnson: … Introduction - a retrospective viewpoint White & Chan: Basic Principles Chan & White: Basic Procedures Albericio et al: Preparation and Handling of Peptides Containing Methionine and Cysteine Quibell & Johnson: Difficult Peptides Wellings et al: Synthesis of Modified Peptides White: Phosphopeptide Synthesis Kihlberg: Glycopeptide Synthesis Barlos & Gatos: Convergent Peptide Synthesis Drijfhout & Hoogerhout: Methods of Preparing Peptide-carrier Conguates Tam & Lu: Chemoselective and Orthogonal Ligation Techniques Mascagni: Purification of Large Peptides Using Chemioselective Tags Cammish & Kates: Instrumentation for Automated Solid-Phase Peptide Synthesis Doerner et al: Manual Multiple Synthesis Methods.

Turns in Peptides and Proteins

1985-01-01

George D. Rose , Lila M. Glerasch , John A. Smith

Reagents for Organic Synthesis

1976-05-01

Richard C. Larock

A gas-liquid solid phase peptide and protein sequenator.

1981-08-01

Rodney M. Hewick , Michael W. Hunkapiller , Leroy Hood +1 more

A new miniaturized protein and peptide sequenator has been constructed which uses gas phase reagents at the coupling and cleavage steps of the Edman degradation. The sample is embedded in … A new miniaturized protein and peptide sequenator has been constructed which uses gas phase reagents at the coupling and cleavage steps of the Edman degradation. The sample is embedded in a matrix of Polybrene dried onto a porous glass fiber disc located in a small cartridge-style reaction cell. The protein or peptide, though not covalently attached to the support, is essentially immobile throughout the degradative cycle, since only relatively apolar, liquid phase solvents pass through the cell. This instrument can give useful sequence data on as little as 5 pmol or protein, can perform extended sequence runs (greater than 30 residues) on subnanomole quantities of proteins purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and can sequence hydrophobic peptides to completion. The sequenator is characterized by a high repetitive yield during the degradation, low reagent consumption, low maintenance requirements, and a degradative cycle time of only 50 min using a complete double cleavage program.

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The Future of Peptide‐based Drugs

2012-12-17

David J. Craik , David P. Fairlie , Spiros Liras +1 more

The suite of currently used drugs can be divided into two categories – traditional ‘small molecule’ drugs with typical molecular weights of <500 Da but with oral bioavailability, and much … The suite of currently used drugs can be divided into two categories – traditional ‘small molecule’ drugs with typical molecular weights of <500 Da but with oral bioavailability, and much larger ‘biologics’ typically >5000 Da that are not orally bioavailable and need to be delivered via injection. Due to their small size, conventional small molecule drugs may suffer from reduced target selectivity that often ultimately manifests in human side‐effects, whereas protein therapeutics tend to be exquisitely specific for their targets due to many more interactions with them, but this comes at a cost of low bioavailability, poor membrane permeability, and metabolic instability. The time has now come to reinvestigate new drug leads that fit between these two molecular weight extremes, with the goal of combining advantages of small molecules (cost, conformational restriction, membrane permeability, metabolic stability, oral bioavailability) with those of proteins (natural components, target specificity, high potency). This article uses selected examples of peptides to highlight the importance of peptide drugs, some potential new opportunities for their exploitation, and some difficult challenges ahead in this field.

Helical Polymers: Synthesis, Structures, and Functions

2009-11-11

Eiji Yashima , Katsuhiro Maeda , Hiroki Iida +2 more

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTHelical Polymers: Synthesis, Structures, and FunctionsEiji Yashima*†, Katsuhiro Maeda‡, Hiroki Iida†, Yoshio Furusho†, and Kanji Nagai†§View Author Information Department of Molecular Design and Engineering, Graduate School of … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTHelical Polymers: Synthesis, Structures, and FunctionsEiji Yashima*†, Katsuhiro Maeda‡, Hiroki Iida†, Yoshio Furusho†, and Kanji Nagai†§View Author Information Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan, and Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan* E-mail: [email protected]†Nagoya University.‡Kanazawa University.§Present address: Department of Applied Chemistry, Graduate School of Engineering, Nagoya University.Cite this: Chem. Rev. 2009, 109, 11, 6102–6211Publication Date (Web):November 11, 2009Publication History Received23 April 2009Published online11 November 2009Published inissue 11 November 2009https://pubs.acs.org/doi/10.1021/cr900162qhttps://doi.org/10.1021/cr900162qreview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views34066Altmetric-Citations1462LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical structure,Conformation,Polymerization,Polymers,Solvents Get e-Alerts

Asymmetric 1,3-Dipolar Cycloaddition Reactions

1998-03-14

Kurt V. Gothelf , Karl Anker Jørgensen

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric 1,3-Dipolar Cycloaddition ReactionsKurt V. Gothelf and Karl Anker JørgensenView Author Information Center for Metal Catalyzed Reactions, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark Cite … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric 1,3-Dipolar Cycloaddition ReactionsKurt V. Gothelf and Karl Anker JørgensenView Author Information Center for Metal Catalyzed Reactions, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark Cite this: Chem. Rev. 1998, 98, 2, 863–910Publication Date (Web):March 14, 1998Publication History Received2 October 1997Revised20 November 1997Published online14 March 1998Published inissue 1 April 1998https://pubs.acs.org/doi/10.1021/cr970324ehttps://doi.org/10.1021/cr970324eresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views17842Altmetric-Citations1749LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical reactions,Hydrocarbons,Molecular structure,Nitrogen compounds,Selectivity Get e-Alerts

Privileged Chiral Catalysts

2003-03-13

Tehshik P. Yoon , Eric N. Jacobsen

One of the most active current areas of chemical research is centered on how to synthesize handed (chiral) compounds in a selective manner, rather than as mixtures of mirror-image forms … One of the most active current areas of chemical research is centered on how to synthesize handed (chiral) compounds in a selective manner, rather than as mixtures of mirror-image forms (enantiomers) with different three-dimensional structures (stereochemistries). Nature points the way in this endeavor: different enantiomers of a given biomolecule can exhibit dramatically different biological activities, and enzymes have therefore evolved to catalyze reactions with exquisite selectivity for the formation of one enantiomeric form over the other. Drawing inspiration from these natural catalysts, chemists have developed a variety of synthetic small-molecule catalysts that can achieve levels of selectivity approaching, and in some cases matching, those observed in enzymatic reactions.

Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides

1970-04-01

E. T. Kaiser , Robert L. Colescott , C.D. Bossinger +1 more

A new method for sequencing DNA.

1977-02-01

Allan M. Maxam , Wendy V. Gilbert

DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify … DNA can be sequenced by a chemical procedure that breaks a terminally labeled DNA molecule partially at each repetition of a base. The lengths of the labeled fragments then identify the positions of that base. We describe reactions that cleave DNA preferentially at guanines, at adenines, at cytosines and thymines equally, and at cytosines alone. When the products of these four reactions are resolved by size, by electrophoresis on a polyacrylamide gel, the DNA sequence can be read from the pattern of radioactive bands. The technique will permit sequencing of at least 100 bases from the point of labeling.

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A Protein Binding Assay for Adenosine 3′:5′-Cyclic Monophosphate

1970-09-01

Alfred G. Gilman

A simple and sensitive assay for adenosine 3′:5′-cyclic monophosphate (cAMP) has been developed that is based on competition for protein binding of the nucleotide, presumably to a cAMP-dependent protein kinase. … A simple and sensitive assay for adenosine 3′:5′-cyclic monophosphate (cAMP) has been developed that is based on competition for protein binding of the nucleotide, presumably to a cAMP-dependent protein kinase. The nucleotide-protein complex is adsorbed on a cellulose ester filter. Assay conditions are such that a binding constant approaching 10 -9 M is obtained, and the assay is thus sensitive to 0.05-0.10 pmol of cAMP.

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Energy transfer: a spectroscopic ruler.

1967-08-01

Lubert Stryer , R P Haugland

Electronic excitation energy transfer as function of distance measured, noting energy transfer process use as spectroscopic ruler Electronic excitation energy transfer as function of distance measured, noting energy transfer process use as spectroscopic ruler

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Amide bond formation: beyond the myth of coupling reagents

2008-12-04

Eric Valeur , Mark Bradley

Amide bond formation is a fundamentally important reaction in organic synthesis, and is typically mediated by one of a myriad of so-called coupling reagents. This critical review is focussed on … Amide bond formation is a fundamentally important reaction in organic synthesis, and is typically mediated by one of a myriad of so-called coupling reagents. This critical review is focussed on the most recently developed coupling reagents with particular attention paid to the pros and cons of the plethora of "acronym" based reagents. It aims to demystify the process allowing the chemist to make a sensible and educated choice when carrying out an amide coupling reaction (179 references).

C−F Bond Activation in Organic Synthesis

2009-03-30

Hideki Amii , Kenji Uneyama

ADVERTISEMENT RETURN TO ISSUEPREVReviewC−F Bond Activation in Organic SynthesisHideki Amii*† and Kenji Uneyama*‡View Author Information Department of Chemistry, Graduate School of Science, Kobe University, Kobe 657-8501, Japan, and Department of … ADVERTISEMENT RETURN TO ISSUEPREVReviewC−F Bond Activation in Organic SynthesisHideki Amii*† and Kenji Uneyama*‡View Author Information Department of Chemistry, Graduate School of Science, Kobe University, Kobe 657-8501, Japan, and Department of Applied Chemistry, Faculty of Engineering, Okayama Univeristy, Okayama 700-8530, Japan* To whom correspondence should be addressed. Phone: 81-78-803-5799. Fax: 81-78-803-5799. E-mail: [email protected] and [email protected]†Kobe University.‡Okayama University.Cite this: Chem. Rev. 2009, 109, 5, 2119–2183Publication Date (Web):March 30, 2009Publication History Received27 June 2008Published online30 March 2009Published inissue 13 May 2009https://pubs.acs.org/doi/10.1021/cr800388chttps://doi.org/10.1021/cr800388creview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views39252Altmetric-Citations1300LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Aromatic compounds,Chemical reactions,Cross coupling reaction,Substitution reactions Get e-Alerts

Rules for ring closure

1976-01-01

Jack E. Baldwin

Three rules which have been found useful, on an empirical basis, to predict the relative facility of ring forming reactions are presented; the physical bases of such rules are described. Three rules which have been found useful, on an empirical basis, to predict the relative facility of ring forming reactions are presented; the physical bases of such rules are described.

β-Peptides: From Structure to Function

2001-10-01

Richard P. Cheng , Samuel H. Gellman , William F. DeGrado

ADVERTISEMENT RETURN TO ISSUEPREVArticleβ-Peptides: From Structure to FunctionRichard P. Cheng, Samuel H. Gellman, and William F. DeGradoView Author Information Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania … ADVERTISEMENT RETURN TO ISSUEPREVArticleβ-Peptides: From Structure to FunctionRichard P. Cheng, Samuel H. Gellman, and William F. DeGradoView Author Information Johnson Research Foundation, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, and Department of Chemistry, University of Wisconsin at Madison, Madison, Wisconsin 53706 Cite this: Chem. Rev. 2001, 101, 10, 3219–3232Publication Date (Web):October 10, 2001Publication History Received27 June 2001Published online10 October 2001Published inissue 1 October 2001https://pubs.acs.org/doi/10.1021/cr000045ihttps://doi.org/10.1021/cr000045iresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views12760Altmetric-Citations1704LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Amides,Chemical structure,Conformation,Monomers,Peptides and proteins Get e-Alerts

Rethinking amide bond synthesis

2011-12-01

Vijaya R. Pattabiraman , Jeffrey W. Bode

Solid Phase Peptide Synthesis

1976-01-01

John Morrow Stewart

Abstract The last two decades have been an era of rapid progress in peptide research. This era was begun by the work of Sanger on the amino acid sequence determination … Abstract The last two decades have been an era of rapid progress in peptide research. This era was begun by the work of Sanger on the amino acid sequence determination of insulin and by du Vigneaud on the structure determination and synthesis of oxytocin. This period has seen impressive progress in the structure elucidation and synthesis of many peptides of natural origin and of great biological significance, as well as in methods for sequence determination and chemical synthesis of peptides [1–4]. Perfection of techniques and instruments for automatic determination of the amino acid sequence of peptides and proteins has made possible a greatly broadened understanding of genetics and evolution as well as the more chemical areas of mechanism of action of enzymes and hormones, and physical chemistry of peptides and proteins. Effective methods of peptide synthesis are crucial to progress in this area, because only by synthesis can adequate amounts of important peptides be made available for chemical, biological, and physical studies, as well as for exploration of the structure-function aspects of biological molecules. In general, progress in peptide synthesis has lagged far behind that in amino acid sequence determination. This is not surprising since effective peptide synthesis requires a very sophisticated system of selectively removable protecting groups for functions of the amino acids involved, and the synthesis of a large heteropolytner of defined sequence requires near perfection of each one of the many steps of the assembly. The classical approach to peptide synthesis, using standard organic chemical methods of synthesis and purification of intermediates, has yielded impressive results during these two decades. However, the special problems associated with the assembly of large molecules make staggering investments in time and materials necessary for the synthesis of large peptides or proteins by classical methods.

Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids

1990-03-01

Gregg Fields , Richard L. Noble

9‐Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been … 9‐Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly “orthogonal” scheme, and thus offers many unique opportunities for bioorganic chemistry.

A synthetic method for formyl→ethynyl conversion (RCHO→RCCH or RCCR′)

1972-01-01

E. J. Corey , P.L. Fuchs

Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery

1991-11-01

Richard A. Houghten , Clemencia Pinilla , Sylvie E. Blondelle +3 more

A Field Guide to Foldamers

2001-12-01

David J. Hill , Matthew J. Mio , Ryan B. Prince +2 more

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Field Guide to FoldamersDavid J. Hill, Matthew J. Mio, Ryan B. Prince, Thomas S. Hughes, and Jeffrey S. MooreView Author Information Roger Adams Laboratory, Departments of … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Field Guide to FoldamersDavid J. Hill, Matthew J. Mio, Ryan B. Prince, Thomas S. Hughes, and Jeffrey S. MooreView Author Information Roger Adams Laboratory, Departments of Chemistry and Materials Science & Engineering, The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801; Department of Chemistry, Macalester College, 1600 Grand Avenue, St. Paul, Minnesota 55105; and 3M Adhesive Technology Center, 3M Center, 201-3N-04, St. Paul, Minnesota 55144 Cite this: Chem. Rev. 2001, 101, 12, 3893–4012Publication Date (Web):December 12, 2001Publication History Received5 September 2001Published online12 December 2001Published inissue 1 December 2001https://pubs.acs.org/doi/10.1021/cr990120thttps://doi.org/10.1021/cr990120tresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views18727Altmetric-Citations2096LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Chemical structure,Conformation,Foldamers,Genetics,Oligomers Get e-Alerts

Selective reactions using allylic metals

1993-09-01

Yoshinori Yamamoto , Naoki Asao

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reactions using allylic metalsYoshinori. Yamamoto and Naoki. AsaoCite this: Chem. Rev. 1993, 93, 6, 2207–2293Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective reactions using allylic metalsYoshinori. Yamamoto and Naoki. AsaoCite this: Chem. Rev. 1993, 93, 6, 2207–2293Publication Date (Print):September 1, 1993Publication History Published online1 May 2002Published inissue 1 September 1993https://pubs.acs.org/doi/10.1021/cr00022a010https://doi.org/10.1021/cr00022a010research-articleACS PublicationsRequest reuse permissionsArticle Views7595Altmetric-Citations1432LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Principles that Govern the Folding of Protein Chains

1973-07-20

Christian B. Anfinsen

2,58835MetricsTotal Downloads2,921Last 6 Months612Last 12 Months1,198Total Citations35Last 6 Months0Last 12 Months0View all metrics 2,58835MetricsTotal Downloads2,921Last 6 Months612Last 12 Months1,198Total Citations35Last 6 Months0Last 12 Months0View all metrics

Synthetic therapeutic peptides: science and market

2009-10-31

Patrick Vlieghe , Vincent Lisowski , Jean Martínez +1 more

LTP and LTD

2004-09-01

Robert C. Malenka , Mark F. Bear

Fluorescamine: A Reagent for Assay of Amino Acids, Peptides, Proteins, and Primary Amines in the Picomole Range

1972-11-24

Sidney Udenfriend , Stanley J. Stein , Peter Böhlen +3 more

Fluorescamine is a new reagent for the detection of primary amines in the picomole range. Its reaction with amines is almost instantaneous at room temperature in aqueous media. The products … Fluorescamine is a new reagent for the detection of primary amines in the picomole range. Its reaction with amines is almost instantaneous at room temperature in aqueous media. The products are highly fluorescent, whereas the reagent and its degradation products are nonfluorescent. Applications are discussed.

Synthesis and Applications of Small Molecule Libraries

1996-01-01

Lorin A. Thompson , Jonathan A. Ellman

ADVERTISEMENT RETURN TO ISSUEPREVArticleSynthesis and Applications of Small Molecule LibrariesLorin A. Thompson and Jonathan A. EllmanView Author Information Department of Chemistry, University of California, Berkeley, California 94720 Cite this: Chem. … ADVERTISEMENT RETURN TO ISSUEPREVArticleSynthesis and Applications of Small Molecule LibrariesLorin A. Thompson and Jonathan A. EllmanView Author Information Department of Chemistry, University of California, Berkeley, California 94720 Cite this: Chem. Rev. 1996, 96, 1, 555–600Publication Date (Web):February 1, 1996Publication History Received17 August 1995Revised18 October 1995Published online1 February 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/cr9402081https://doi.org/10.1021/cr9402081research-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views5148Altmetric-Citations1300LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Amines,Monomers,Organic polymers,Peptides and proteins,Reaction products Get e-Alerts

Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery

2000-03-17

Stuart L. Schreiber

Modern drug discovery often involves screening small molecules for their ability to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused libraries), … Modern drug discovery often involves screening small molecules for their ability to bind to a preselected protein target. Target-oriented syntheses of these small molecules, individually or as collections (focused libraries), can be planned effectively with retrosynthetic analysis. Drug discovery can also involve screening small molecules for their ability to modulate a biological pathway in cells or organisms, without regard for any particular protein target. This process is likely to benefit in the future from an evolving forward analysis of synthetic pathways, used in diversity-oriented synthesis, that leads to structurally complex and diverse small molecules. One goal of diversity-oriented syntheses is to synthesize efficiently a collection of small molecules capable of perturbing any disease-related biological pathway, leading eventually to the identification of therapeutic protein targets capable of being modulated by small molecules. Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.

Fluorescence reaction for amino acids

1971-06-01

Marc Roth

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescence reaction for amino acidsMarc. RothCite this: Anal. Chem. 1971, 43, 7, 880–882Publication Date (Print):June 1, 1971Publication History Published online1 May 2002Published inissue 1 June 1971https://pubs.acs.org/doi/10.1021/ac60302a020https://doi.org/10.1021/ac60302a020research-articleACS PublicationsRequest … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescence reaction for amino acidsMarc. RothCite this: Anal. Chem. 1971, 43, 7, 880–882Publication Date (Print):June 1, 1971Publication History Published online1 May 2002Published inissue 1 June 1971https://pubs.acs.org/doi/10.1021/ac60302a020https://doi.org/10.1021/ac60302a020research-articleACS PublicationsRequest reuse permissionsArticle Views5563Altmetric-Citations1121LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Foldamers: A Manifesto

1998-03-13

Samuel H. Gellman

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFoldamers: A ManifestoSamuel H. GellmanView Author Information Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 Cite this: Acc. Chem. Res. 1998, 31, 4, 173–180Publication Date (Web):March … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFoldamers: A ManifestoSamuel H. GellmanView Author Information Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 Cite this: Acc. Chem. Res. 1998, 31, 4, 173–180Publication Date (Web):March 13, 1998Publication History Received6 October 1997Published online13 March 1998Published inissue 1 April 1998https://pubs.acs.org/doi/10.1021/ar960298rhttps://doi.org/10.1021/ar960298rresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views12005Altmetric-Citations2294LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Conformation,Foldamers,Nucleic acid structure,Oligomers,Peptides and proteins Get e-Alerts

Amide bond formation and peptide coupling

2005-09-20

Christian Montalbetti , Virginie M. Falque

Eine neue Methode zur Synthese von Peptiden: Aktivierung der Carboxylgruppe mit Dicyclohexylcarbodiimid unter Zusatz von 1‐Hydroxy‐benzotriazolen

1970-03-01

Wolfgang König , Rolf Geiger

1-Hydroxy-benzotriazol sowie verschiedene kernsubstituierte 1-Hydroxy-benzotriazole eignen sich als Zusätze bei der Dicyclohexylcarbodiimid-Methode zur Synthese von Peptiden. Ihr Einfluß auf die Racemisierung bei Peptidsynthesen wurde unter Anwendung des gaschromatographischen Racemisierungstests von … 1-Hydroxy-benzotriazol sowie verschiedene kernsubstituierte 1-Hydroxy-benzotriazole eignen sich als Zusätze bei der Dicyclohexylcarbodiimid-Methode zur Synthese von Peptiden. Ihr Einfluß auf die Racemisierung bei Peptidsynthesen wurde unter Anwendung des gaschromatographischen Racemisierungstests von Weygand u. Mitarbb.2) untersucht. Die neuen Zusätze senken die Racemisierung, verhindern die N-Acyl-harnstoffbildung und führen in hoher Ausbeute zu sehr reinen Peptiden. A New Method for Synthesis of Peptides: Activation of the Carboxyl Group with Dicyclohexylcarbodiimide using 1-hydroxybenzotriazoles as Additives 1-Hydroxybenzotriazole and a number of substituted 1-Hydroxybenzotriazoles are suitable additives in the synthesis of peptides using the dicyclohexylcarbodiimide method1). The glc-racemisation test described by Weygand and coworkers2) was used to determine the influence of these additives on the racemisation during peptide synthesis. The newly employed additives decrease racemisation, prohibit the formation of N-acylurea and afford peptides in excellent yield and a high state of purity.

Pyrrolidinyl-Spirooxindole Natural Products as Inspirations for the Development of Potential Therapeutic Agents

2007-10-17

Chris V. Galliford , Karl A. Scheidt

The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties. Significant recent … The 3,3'-pyrrolidinyl-spirooxindole unit is a privileged heterocyclic motif that forms the core of a large family of alkaloid natural products with strong bioactivity profiles and interesting structural properties. Significant recent advances in the synthesis of this fused heterocyclic system have led to intense interest in the development of related compounds as potential medicinal agents or biological probes.

A Planning Strategy for Diversity‐Oriented Synthesis

2003-12-17

Martin D. Burke , Stuart L. Schreiber

In contrast to target-oriented synthesis (TOS) and medicinal or combinatorial chemistry, which aim to access precise or dense regions of chemistry space, diversity-oriented synthesis (DOS) populates chemical space broadly with … In contrast to target-oriented synthesis (TOS) and medicinal or combinatorial chemistry, which aim to access precise or dense regions of chemistry space, diversity-oriented synthesis (DOS) populates chemical space broadly with small-molecules having diverse structures. The goals of DOS include the development of pathways leading to the efficient (three- to five-step) synthesis of collections of small molecules having skeletal and stereochemical diversity with defined coordinates in chemical space. Ideally, these pathways also yield compounds having the potential to attach appendages site- and stereoselectively to a variety of attachment sites during a post-screening, maturation stage. The diverse skeletons and stereochemistries ensure that the appendages can be positioned in multiple orientations about the surface of the molecules. TOS as well as medicinal and combinatorial chemistries have been advanced by the development of retrosynthetic analysis. Although the distinct goals of DOS do not permit the application of retrosynthetic concepts and thinking, these foundations are being built on, by using parallel logic, to develop a complementary procedure known as forward-synthetic analysis. This analysis facilitates synthetic planning, communication, and teaching in this evolving discipline.

Privileged scaffolds for library design and drug discovery

2010-03-22

Matthew Welsch , Scott A. Snyder , Brent R. Stockwell

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SH2 domains recognize specific phosphopeptide sequences

1993-03-12

Zhou Songyang , Steven E. Shoelson , Manas K. Chaudhuri +7 more

Peptide Folding: When Simulation Meets Experiment

1999-01-15

Xavier Daura , Karl Gademann , Bernhard Jaun +3 more

Accurate reproduction of the mechanism of peptide folding in solution and conformational preferences as a function of amino acid sequence is possible with atomic level dynamics simulations. For example, the … Accurate reproduction of the mechanism of peptide folding in solution and conformational preferences as a function of amino acid sequence is possible with atomic level dynamics simulations. For example, the simulations correctly predict a left-handed 31-helical fold for the β-heptapeptide 1 (the molecular model is shown in the picture) and a right-handed helical fold for the β-hexapeptide 2, as was confirmed by NMR spectroscopy.

A highly sensitive adenylate cyclase assay

1974-04-01

Yoram Salomon , Constantine Londos , Martin Rodbell

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Analysis of Past and Present Synthetic Methodologies on Medicinal Chemistry: Where Have All the New Reactions Gone?

2015-11-16

Dean G. Brown , Jonas Boström

An analysis of chemical reactions used in current medicinal chemistry (2014), three decades ago (1984), and in natural product total synthesis has been conducted. The analysis revealed that of the … An analysis of chemical reactions used in current medicinal chemistry (2014), three decades ago (1984), and in natural product total synthesis has been conducted. The analysis revealed that of the current most frequently used synthetic reactions, none were discovered within the past 20 years and only two in the 1980s and 1990s (Suzuki-Miyaura and Buchwald-Hartwig). This suggests an inherent high bar of impact for new synthetic reactions in drug discovery. The most frequently used reactions were amide bond formation, Suzuki-Miyaura coupling, and SNAr reactions, most likely due to commercial availability of reagents, high chemoselectivity, and a pressure on delivery. We show that these practices result in overpopulation of certain types of molecular shapes to the exclusion of others using simple PMI plots. We hope that these results will help catalyze improvements in integration of new synthetic methodologies as well as new library design.

A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminases

1957-07-01

Stanley Reitman , Sam Frankel

Journal Article A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminases Get access Stanley Reitman, M.D., Stanley Reitman, M.D. Medical and Laboratory Sections, Research Institute, … Journal Article A Colorimetric Method for the Determination of Serum Glutamic Oxalacetic and Glutamic Pyruvic Transaminases Get access Stanley Reitman, M.D., Stanley Reitman, M.D. Medical and Laboratory Sections, Research Institute, The Jewish Hospital of St. Louis, St. Louis, Missouri Search for other works by this author on: Oxford Academic Google Scholar Sam Frankel, Ph.D. Sam Frankel, Ph.D. Medical and Laboratory Sections, Research Institute, The Jewish Hospital of St. Louis, St. Louis, Missouri Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 28, Issue 1, 1 July 1957, Pages 56–63, https://doi.org/10.1093/ajcp/28.1.56 Published: 01 July 1957 Article history Received: 31 December 1956 Revision received: 11 March 1957 Accepted: 01 April 1957 Published: 01 July 1957

Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide

1963-07-01

R. B. Merrifield

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid Phase Peptide Synthesis. I. The Synthesis of a TetrapeptideR. B. MerrifieldCite this: J. Am. Chem. Soc. 1963, 85, 14, 2149–2154Publication Date (Print):July 1, 1963Publication History Published … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid Phase Peptide Synthesis. I. The Synthesis of a TetrapeptideR. B. MerrifieldCite this: J. Am. Chem. Soc. 1963, 85, 14, 2149–2154Publication Date (Print):July 1, 1963Publication History Published online1 May 2002Published inissue 1 July 1963https://doi.org/10.1021/ja00897a025Request reuse permissionsArticle Views34406Altmetric-Citations6225LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (944 KB) Get e-Alertsclose Get e-Alerts

Therapeutic peptides: Historical perspectives, current development trends, and future directions

2017-07-02

Jolene L. Lau , Michael K. Dunn

Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and … Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. We maintain a comprehensive dataset on peptides that have entered human clinical studies that includes over 150 peptides in active development today. Here we provide an overview of the peptide therapeutic landscape, including historical perspectives, molecular characteristics, regulatory benchmarks, and a therapeutic area breakdown.

Handbook of operant behavior

1978-06-01

Ralph M. Turner

Trends in peptide drug discovery

2021-02-03

Markus Muttenthaler , Glenn F. King , David J. Adams +1 more

Manuscript Preparation

1997-10-01

Therapeutic peptides: current applications and future directions

2022-02-14

Lei Wang , Nanxi Wang , Wenping Zhang +6 more

Abstract Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and … Abstract Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.

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Synthesis of Proteins by Native Chemical Ligation

1994-11-04

Philip E. Dawson , Tom W. Muir , Ian Clark‐Lewis +1 more

A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. … A simple technique has been devised that allows the direct synthesis of native backbone proteins of moderate size. Chemoselective reaction of two unprotected peptide segments gives an initial thioester-linked species. Spontaneous rearrangement of this transient intermediate yields a full-length product with a native peptide bond at the ligation site. The utility of native chemical ligation was demonstrated by the one-step preparation of a cytokine containing multiple disulfides. The polypeptide ligation product was folded and oxidized to form the native disulfide-containing protein molecule. Native chemical ligation is an important step toward the general application of chemistry to proteins.

Insertion of anthranilyl unit into inert amides: A facile route to oligoamides and cyclic peptides

2025-06-25

Daoshun Wu , Kaili Xie , Yunfang Sun +5 more | Science Advances

Manipulation of polar functional groups to extend the druggability and developability space is an important approach in the current field of drug discovery. Here, we report an editing method that … Manipulation of polar functional groups to extend the druggability and developability space is an important approach in the current field of drug discovery. Here, we report an editing method that enables the direct insertion of anthranilyl units into inert amides to form versatile oligoamides and cyclic peptides under exceptionally mild reaction conditions. We showcase a diverse array of pharmaceuticals, natural products, and bioactive molecules involving the mentioned scaffold insertion. The synthesis of the secondary metabolites from marine-derived fungi, the expedited construction of bioactive molecules, and the assembly of functionalized peptide macrocycles through iterative insertions highlight the synthetic utility of this method. Computational tools and experimental measurements indicate that a hydrogen bond network formed by reacting and catalytic amide enables the insertion of the anthranilyl unit into a C─N bond.

Facilitating the Isolation of Polar Natural Products: Mild 1,1’‐Carbonyldiimidazole‐Enabled Method for Derivatization of Acids and Alcohols

2025-06-25

Moses Mutuse Mutungi , Curtis C. Ho , Alex C. Bissember +1 more | European Journal of Organic Chemistry

Many secondary metabolites containing carboxylic acid and alcohol functional groups are highly polar and can be difficult to purify and isolate from complex extracts obtained from natural sources. The conversion … Many secondary metabolites containing carboxylic acid and alcohol functional groups are highly polar and can be difficult to purify and isolate from complex extracts obtained from natural sources. The conversion of these natural products to their corresponding alkyl esters/ carbonates under mild conditions can simplify their purification and isolation. However, traditional derivatization methods have often relied on toxic and/ or corrosive reagents that can also lead to byproduct formation or epimerization in some instances. In this work, 1,1′‐carbonyldiimidazole (CDI), a relatively inexpensive reagent with inherently low toxicity, is utilized to activate polar natural products containing carboxylic acids and alcohols to enable the formation of less polar species (N‐acylimidazoles and N‐acyloxymidazoles). These intermediates are readily converted into methyl esters and carbonates by treatment with methanol. It is anticipated that this rather simple and versatile derivatization method can facilitate the efficient isolation of secondary metabolites bearing polar carboxylic acid and alcohol residues.

Development of Semisynthesis to Achieve Sulfonium Proteins with Diverse Modifications

2025-06-25

Jin‐Yu Terence Yang , Jianxiang Wei , Mingxuan Wu | Organic Letters

Recent advances in sulfonium peptides have demonstrated their potential to study post-translational modifications and protein-protein interactions, owing to the site-selective cross-linking to tryptophan and tyrosine. However, current synthetic methods cannot … Recent advances in sulfonium peptides have demonstrated their potential to study post-translational modifications and protein-protein interactions, owing to the site-selective cross-linking to tryptophan and tyrosine. However, current synthetic methods cannot meet the demand to prepare full-length sulfonium proteins with multiple modifications that mimic cellular scenarios. Here we report a semisynthesis method to address these challenges. We first developed an orthogonal protecting strategy that enables the site-specific incorporation of sulfonium into peptide fragments containing multiple cysteines. After characterization of sulfonium stability in aqueous solutions, the semisynthesis of sulfonium proteins was achieved by native chemical ligation and sortase-mediated ligation. This work expands sulfonium tools to complicated protein levels for diverse biological studies.

Amide Chemistry Enables Redox Locking of Cyclic Disulfides for Polypeptide Assembly

2025-06-24

Vincent Diemer , Eliott Roy , Benoît Snella +2 more | Angewandte Chemie International Edition

A practical strategy in synthetic organic chemistry for shutting down temporarily the nucleophilicity of thiols is to exploit their redox properties by converting them into disulfides. The stability of such … A practical strategy in synthetic organic chemistry for shutting down temporarily the nucleophilicity of thiols is to exploit their redox properties by converting them into disulfides. The stability of such a thiol protection in reductive medium can be sensitive to microenvironmental changes, including chemical modifications occurring nearby. Although difficult to achieve, large shifts in disulfide stability might provide a practical mean for bringing selectivity in a reacting system comprising multiple thiol functionalities. Here we report that the stability of a cyclic disulfide increases dramatically upon acylation of an amino group placed in the vicinity of the S‐S bond. The gain in stability is so pronounced that the amide bond formation acts as a redox lock. We describe the application of such a redox switch to the chemoselective assembly of polypeptides by thiol‐based peptide ligation chemistries.

Multicolumn Two-Dimensional Liquid Chromatography Screening Platform for Stereopeptidomics and Application to Antimicrobial Peptide Polyene and Lipopeptide

2025-06-24

Cornelius Knappe , Simon Jaag , Taulant Dema +5 more | Analytical Chemistry

Therapeutic peptides are a rapidly growing field in research and drug development. While the majority of natural and synthetic therapeutic peptides have l-amino acids as building blocks, d-amino acid-containing peptides … Therapeutic peptides are a rapidly growing field in research and drug development. While the majority of natural and synthetic therapeutic peptides have l-amino acids as building blocks, d-amino acid-containing peptides are found frequently in nonribosomal peptides or can be formed during peptide synthesis by epimerization. Thus, analytical methods are needed for the quality control of stereointegrity and the determination of absolute configurations. Enantioselective amino acid analysis following complete hydrolysis is indispensable in the field but leads to the loss of sequence information, i.e., the position of d-amino acids can no longer be unambiguously assigned. Here, we propose a multicolumn two-dimensional liquid chromatography-tandem high-resolution mass spectrometry (2D LC-HRMS) platform with multiple reversed-phase type columns (C18, charged surface hybrid C18, mixed-mode C18 AX) in the first dimension (1D) and multiple chiral columns in the second dimension (2D) (teicoplanin, teicoplanin aglycone, crown ether, and zwitterionic quinine and quinidine carbamate-based chiral stationary phases). It allows the combination of distinct 1D columns (for peptide epimer/diastereomer separations) and 2D columns (for peptide enantiomer separations), enabling the full resolution of complex peptide stereoisomer mixtures. The utility of this 2D-LC platform for peptide analyses was demonstrated for a tetrapeptide amide from an antimicrobial peptide polyene natural product and a lipopeptide, digested into dipeptides for middle-down/middle-up stereoselective peptide analysis. Multiple heart-cutting and selective comprehensive 2D-LC, respectively, with active solvent modulation and sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) enabled the full separation of all stereoisomers and the clarification of the configurations of all sample peptides. Such a 2D-LC-HRMS screening platform can be valuable as an efficient and fast generic approach for streamlining method development in the pharmaceutical industry.

Conformational Study of Synthetic Beta-Amyloid Peptide (25-35) Analogs

2025-06-24

| Deleted Journal

Amide Chemistry Enables Redox Locking of Cyclic Disulfides for Polypeptide Assembly

2025-06-24

Vincent Diemer , Eliott Roy , Benoît Snella +2 more | Angewandte Chemie

Novel Mitsunobu Reagent Enables Stereospecific Substitution of Alcohols with Amines

2025-06-23

| Synfacts

Regioselective Synthesis of Fluorescent Alkoxy-Substituted Phenazines and N-Alkyl Phenazinium Salts

2025-06-23

Paweł Ręka , K. Ostrowska , Jarosław Grolik +3 more | The Journal of Organic Chemistry

A method for the regioselective synthesis of 2,3,7,8-tetraalkoxyphenazines and N-alkyl phenazinium salts was developed. The protocol allows the synthesis of compounds with up to four different substituents at the designed … A method for the regioselective synthesis of 2,3,7,8-tetraalkoxyphenazines and N-alkyl phenazinium salts was developed. The protocol allows the synthesis of compounds with up to four different substituents at the designed positions. The synthesis was achieved using nonsymmetrically substituted 4,5-dialkoxy-2-nitroanilines and 1-bromo-2-nitrobenzenes via Buchwald-Hartwig amination, followed by tandem catalytic reduction and oxidative cyclization. The synthesized derivatives exhibit intense fluorescence in solution, with significant changes in spectroscopic properties induced by solvent polarity, the presence of acids, and changing the counterion in N-alkyl phenazinium salts.

A Mild Protecting-Group Free Strategy for Neoglycoconjugate Synthesis

2025-06-23

P. Raju , Chun‐Hua Dong , Craig R. Garen +2 more | Bioconjugate Chemistry

The synthesis of neoglycoconjugates has paved the way for the discovery of novel probes that mimic natural glycoconjugates and can provide designed research tools and therapeutics. In some cases, the … The synthesis of neoglycoconjugates has paved the way for the discovery of novel probes that mimic natural glycoconjugates and can provide designed research tools and therapeutics. In some cases, the target protein may not be amenable to harsh conditions; therefore, semisynthetic or chemical methods must be chosen with care. Here, we present a simple and modular chemoselective coupling strategy between an unprotected sugar and an N,O-disubstituted hydroxylamine under mild acidic conditions. This strategy removes any need for protecting groups on the glycan. The terminal alkene group of the conjugate serves as an effective handle to allow facile conjugation to the protein of interest via thiol-ene coupling (TEC), with proteins bearing a cysteine or free thiol to prepare neoglycoconjugates. We demonstrate that the strategy is compatible with both N- and O-linked glycans using protecting-group free strategies and optimize the TEC conditions using a variety of photocatalysts. Finally, we test the method on an aggregation-prone protein, α-synuclein. We envision that this strategy could allow the construction of complex glycoconjugates for biological testing using isolated glycans, or for generation of conjugates where the protein of interest is sensitive to harsh conditions.

One-Pot Peptide Synthesis under Neutral Conditions Using Triphenyl Phosphite

2025-06-23

| Synfacts

Photoredox-Catalyzed Synthesis of Unnatural Amino Acids

2025-06-23

| Synfacts

Three-Component Strategy for the Synthesis of Alkyl Nitrile BCP Derivatives

2025-06-23

Jiabin Shen , Lin Li , Qing Pang +4 more | The Journal of Organic Chemistry

Bicyclo[1.1.1]pentanes (BCPs) are important bioisosteres for para-substituted arenes in drug discovery. Herein, we describe a universal and practical protocol for the carbothiolation of [1.1.1]propellane using available AIBN as a cyanoalkyl … Bicyclo[1.1.1]pentanes (BCPs) are important bioisosteres for para-substituted arenes in drug discovery. Herein, we describe a universal and practical protocol for the carbothiolation of [1.1.1]propellane using available AIBN as a cyanoalkyl source via multicomponent reaction. The catalyst- and additive-free conditions, broad functional group tolerance, environmental-friendliness, and simplicity of this procedure make it a valuable strategy for accessing alkyl nitriles BCP derivatives.

Flexible docking of cyclic peptides to proteins using CABS-dock

2025-06-21

M. Zalewski , Aleksandra E. Badaczewska-Dawid , Sebastian Kmiecik | bioRxiv (Cold Spring Harbor Laboratory)

Cyclic peptides are promising therapeutics, but their flexible docking remains challenging. We present a protocol based on the well-established CABS-dock method, enhanced with cyclic restraints and Rosetta refinement. The approach … Cyclic peptides are promising therapeutics, but their flexible docking remains challenging. We present a protocol based on the well-established CABS-dock method, enhanced with cyclic restraints and Rosetta refinement. The approach was evaluated on 38 benchmark complexes previously used in other docking method studies. While selecting the truly best model remains difficult, near-native solutions are frequently sampled. CABS-dock offers global, unbiased docking without prior binding site knowledge, making it valuable for pose generation, structural ensemble modeling, and integration into AI-driven peptide-protein docking workflows.

Protocol for Membrane Permeability Prediction of Cyclic Peptides using Descriptors Obtained from Extended Ensemble Molecular Dynamics Simulations and Chemical Structures

2025-06-21

Masatake Sugita , Yudai Noso , Jianan Li +3 more | bioRxiv (Cold Spring Harbor Laboratory)

Improving membrane permeability is crucial in cyclic peptide drug discovery. Although the approach based on molecular dynamics (MD) simulation is widely used, it is computationally expensive. Alternatively, machine learning can … Improving membrane permeability is crucial in cyclic peptide drug discovery. Although the approach based on molecular dynamics (MD) simulation is widely used, it is computationally expensive. Alternatively, machine learning can predict membrane permeability at negligible cost, but it requires a larger dataset. There are only 7991 experimental values of membrane permeability available at the newly developed database. Another challenge in predicting membrane permeability using machine learning arises from the unique stable conformation of each cyclic peptide, which is strongly related to membrane permeability but difficult to predict from chemical structure. Therefore, we developed a machine learning protocol using 3D descriptors obtained from MD simulations in addition to 2D descriptors obtained from chemical structure of cyclic peptides, respectively, to generate a universal model with a realistic computational cost. We targeted 252 peptides across four datasets and, to calculate their 3D descriptors, predicted their conformation outside the membrane, at the water/membrane interface, and in the membrane by MD simulations based on the replica exchange with solute tempering/replica exchange umbrella sampling method using 16 replicas. For machine learning, six different algorithms were used, ranging from simple methods such as ridge regression to more sophisticated methods such as XGBoost. The best prediction performance was obtained using XGBoost, with a Pearson's correlation coefficient R = 0.77 and root mean square error (RMSE) = 0.62. The important descriptors included those that describe the hydrophilicity and hydrophobicity of the peptide, conformational differences between inside and outside the membrane, and the degree of freedom of the peptide. We confirm the model's ability to predict the membrane permeability of peptides that differ in chemical structure from the training data by predicting the external data consisting of 24 peptides and obtained R = 0.76, RMSE = 1.14. Furthermore, we extracted one of the four datasets of the training data, re-trained the model, and performed the prediction of the permeability coefficients of the extracted dataset. The results showed the model's generic nature with R = 0.61 and RMSE = 0.74, when using position-specific (PS) 3D, and 2D descriptors. In such situations descriptors based on conformations obtained from MD are essential for the prediction.

2-(2-(Benzylamino)-2-Oxoethyl)-1-Methyl-1H-Pyrrole-3-Carboxylic Acid

2025-06-20

Monika Fryc , Beata Gryzło , Pravin Kumar +1 more | Molbank

Here, 2-(2-(Benzylamino)-2-oxoethyl)-1-methyl-1H-pyrrole-3-carboxylic acid was efficiently synthesised in good yield via an amide coupling reaction between 2-carboxymethyl-1-methyl-1H-pyrrole-3-carboxylic acid and benzylamine, employing TBTU as the coupling reagent and DIPEA as the base. … Here, 2-(2-(Benzylamino)-2-oxoethyl)-1-methyl-1H-pyrrole-3-carboxylic acid was efficiently synthesised in good yield via an amide coupling reaction between 2-carboxymethyl-1-methyl-1H-pyrrole-3-carboxylic acid and benzylamine, employing TBTU as the coupling reagent and DIPEA as the base. The reaction was carried out in dichloromethane at room temperature. The compound was characterised by melting point determination, 1H and 13C NMR, IR spectroscopy, and mass spectrometry. The combined analytical data confirm the target molecule’s successful synthesis and structural integrity.

Chemoenzymatic synthesis and in vitro selection of de novo thiazole‐containing macrocyclic peptides

2025-06-20

Akihiro Saito , Hiroyuki Kimura , Hiroyasu Onaka +2 more | Chemistry - A European Journal

Backbone thiazole moieties prevail in bioactive peptidic natural products and play important roles in their biological functions. However, the de novo discovery of artificial thiazole‐containing peptide ligands remains challenging. Here, … Backbone thiazole moieties prevail in bioactive peptidic natural products and play important roles in their biological functions. However, the de novo discovery of artificial thiazole‐containing peptide ligands remains challenging. Here, we report an mRNA display‐based selection platform for thiazole‐containing macrocyclic peptides (ThzteMP), established through a dedicated posttranslational chemoenzymatic transformation. This method exploits the unique reactivity of ribosomally incorporated thioamides, enabling enzyme‐free spontaneous heterocyclization to form thiazoline, which is further oxidized using the substrate‐tolerant azoline dehydrogenase (GodE) to yield a thiazole moiety. By integrating this chemoenzymatic process with chloroacetyl‐mediated thioether macrocyclization and mRNA display, we have successfully discovered thiazole‐containing macrocyclic peptide ligands with high binding affinities against p‐21 activated kinase 4 (PAK4). This study establishes a robust system to expedite ligand discovery of pseudo‐natural peptides and to investigate the functional benefit of their backbone thiazoles.

Aqualigase: A Star Enzyme for One-Step Peptide Bond Dehydration Condensation in a Nature Aqueous Phase

2025-06-20

Yinghui Feng , Xin Yan , Mingzhe Ma +7 more | ACS Catalysis

Investigating the Site‐Specific Impact of Fluorine Substitution on Aromatic Interactions in a Tryptophan Zipper Peptide

2025-06-19

D. Reiter , Ferhat Mutlu , David A. Ebert +4 more | Chemistry - A European Journal

The stability of pairwise tryptophan (Trp) edge‐to‐face aromatic interactions has been exploited in the design of small tryptophan zipper (Trpzip) peptides. Herein, we report a systematic study of the regiospecific … The stability of pairwise tryptophan (Trp) edge‐to‐face aromatic interactions has been exploited in the design of small tryptophan zipper (Trpzip) peptides. Herein, we report a systematic study of the regiospecific impact of four constitutional isomers of non‐natural fluoro‐Trp, regarding their incorporation at either edge‐ or face‐position. Single fluorine substituents withdraw electron density from the indole moiety and introduce a highly electronegative component while the native geometry of Trp is maintained. We employed a library approach based on the sequence of Trpzip2 and assessed peptide structure and stability using CD, FTIR, and NMR spectroscopy. Global hairpin stability was improved or compromised upon site‐specific incorporation of a single monofluoro‐Trp regioisomer. Fluorine substitution revealed key CH/π interactions within the Trp/Trp packing and holds potential for the future optimization of aromatic interactions involving Trp.

Reshaping the Substrate-Binding Pocket of Leucine Dehydrogenase for Efficient Synthesis of <scp>l</scp>-Phenylglycine and Its Substituted Derivatives

2025-06-19

Lu Zhao , Wenhe Zhang , Min Li +7 more | Journal of Agricultural and Food Chemistry

l-Leucine dehydrogenase (LeuDH)-mediated direct asymmetric reduction amination of prochiral α-keto acids represents an ideal approach for the synthesis of l-phenylglycine and its derivatives. However, limited substrate acceptance hinders their applications. … l-Leucine dehydrogenase (LeuDH)-mediated direct asymmetric reduction amination of prochiral α-keto acids represents an ideal approach for the synthesis of l-phenylglycine and its derivatives. However, limited substrate acceptance hinders their applications. Herein, we systematically investigated the substrate acceptance of LeuDHs for benzoylformic acid and its monosubstituted derivatives, revealing the correlation between substrate structure and enzyme activity. Meanwhile, to efficiently augment the LeuDH overall catalytic activity toward monosubstituted benzoylformic acids, we reported a two-stage screening strategy using o-chlorobenzoylformic acid (2e) as the starting screening substrate. A superior mutant library with 10-127-fold enhanced catalytic efficiency toward ortho-(M2-1 (L40V/V294A) and M2-2 (E114V/V294G)) and meta- and para-(M2-4 (E114L/V294G)) substituted benzoylformic acids was generated, and following future backtracking analysis, mutant M2-3 (L40V/T134G) with further increased catalytic activity of meta-substituted substrates was obtained. Furthermore, gram-scale asymmetric synthesis of l-phenylglycine (3a), L-p-fluorophenylglycine (3d), and L-o-chlorophenylglycine (3e) was performed with high substrate loading (1 M) and space-time yields up to 1800, 2016, and 2208 g/L·day, respectively. This study provides efficient biocatalysts for the synthesis of l-phenylglycine and its derivatives and establishes a referable engineering workflow for the collective evolution of amino acid dehydrogenase against differently positioned substituted substrate panels.

Migrative Reductive Amination of Ketones Enabled by Multitasking Reagents

2025-06-19

Artem Khegay , Dennis G. Hall | The Journal of Organic Chemistry

Secondary amines are key synthetic intermediates and constituents of pharmaceutical agents. They are often prepared by the classical reductive amination of ketones and aldehydes, a staple reaction in organic chemistry. … Secondary amines are key synthetic intermediates and constituents of pharmaceutical agents. They are often prepared by the classical reductive amination of ketones and aldehydes, a staple reaction in organic chemistry. Reductive amination forms products without modifying the carbon framework, which restricts its power and breadth. To expand chemical space and access isomeric amines with a rearranged skeleton, a migrative variant was developed by orchestrating three distinct reactions in a single flask, without solvent changes, using two inexpensive and nontoxic reagents: a Zn(II) salt and a hydrosilane. Mechanistic insights confirmed that both reagents are uniquely multitasking ─ active and synergistic ─ across all reaction stages, lending a practical open-flask procedure that embodies many ideals of green chemistry. This method demonstrates a wide scope of acyclic and cyclic ketones and aldehydes with both aliphatic and aromatic groups, including bioactive molecules and macrocyclic natural products isolated with highly favorable E-factor, process mass intensity, and other established greenness metrics. Furthermore, the efficiency of this migrative reductive amination was highlighted in a one-step synthesis of the marine natural product haliclorensin C from l-muscone.

t-BuOLi-promoted Knoevenagel condensation: An efficient approach for synthesizing Arylid-BOX

2025-06-18

Run He , Zilong Zhang , Yuxiang Zhou +3 more | Tetrahedron Letters

Proline-Aromatic Sequences Stabilize Turns via C–H/π Interactions in Both cis-Proline and trans-Proline

2025-06-18

Himal K. Ganguly , Michael Elbaum , Neal J. Zondlo | Biochemistry

In proteins, proline-aromatic sequences exhibit increased frequencies of cis-proline amide bonds, via proposed C-H/π interactions between the aromatic ring and either the proline ring or the backbone C-Hα of the … In proteins, proline-aromatic sequences exhibit increased frequencies of cis-proline amide bonds, via proposed C-H/π interactions between the aromatic ring and either the proline ring or the backbone C-Hα of the residue prior to proline. However, previous bioinformatics studies on proteins and experiments on proline-aromatic sequences in peptides have not revealed a clear correlation between the electronic properties of the aromatic ring and the population of cis-proline. An investigation of the effects of aromatic residue on the conformation of proline-aromatic sequences was conducted using three approaches: NMR spectroscopy in model peptides of the sequence Ac-TGPAr-NH2 (Ar = encoded and unnatural aromatic amino acids); bioinformatics analysis of structures in proline-aromatic sequences in the PDB; and quantum computational investigations. C-H/π and hydrophobic interactions were observed to stabilize local structures in both the trans-proline and cis-proline conformations, with each exhibiting C-H/π interactions between the aromatic ring and Hα of the residue prior to proline and/or with the proline ring. These C-H/π interactions were strongest with tryptophan and weakest with cationic histidine. Aromatic interactions with histidine were modulated in strength by His ionization state. Proline-aromatic sequences were associated with specific conformational poses, including type I and type VI β-turns. C-H/π interactions at the pre-proline Hα, which were stronger than interactions at Pro, stabilize normally less favorable conformations, including the ζ or αL conformations at the pre-proline residue, cis-proline, and/or the g+ χ1 rotamer or αL conformation at the aromatic residue. Proline-aromatic sequences, especially Pro-Trp sequences, are loci to nucleate turns, helices, loops, and other local structures in proteins.

Function without form in synthetic polymers mimicking protein hydration

2025-06-18

Michael Webb | Nature Chemistry

Preparation of 211At-Labeled (Hetero)aryl Compounds from Triarylsulfonium and Dibenzothiophenium Salts

2025-06-18

Clémence Maingueneau , Romain Eychenne , Jean‐François Gestin +1 more | Organic Letters

211At-labeled (hetero)aryl compounds were obtained from arylsulfonium salt in high RCY with a short reaction time. Benzothiophenium salts appear to be superior to triarylsulfonium salts with a high efficiency demonstrated … 211At-labeled (hetero)aryl compounds were obtained from arylsulfonium salt in high RCY with a short reaction time. Benzothiophenium salts appear to be superior to triarylsulfonium salts with a high efficiency demonstrated on electronically enriched or depleted phenyl rings and an ortho-substituted substrate. As a potential application, a 211At-labeled benzylazide prosthetic group was produced and conjugated to octreotate by SPAAC. This procedure offers an alternative to previous approaches that generally require toxic or unstable precursors and/or catalysts, and/or lead to inseparable products.

Selective Oxidation of Disparate Functional Groups Mediated by a Common Aspartic Acid-Based Peptide Catalyst Platform

2025-06-18

S. Huth , Elizabeth A. Stone , Scott J. Miller | Accounts of Chemical Research

ConspectusAs drug molecules become increasingly complex, the need to develop new or improved strategies for the efficient and selective synthesis and editing of bioactive compounds grows. Inspired by the high … ConspectusAs drug molecules become increasingly complex, the need to develop new or improved strategies for the efficient and selective synthesis and editing of bioactive compounds grows. Inspired by the high selectivity and fast rates exhibited in many enzymatic reactions to assemble complex natural products, our group and others have developed peptide-based catalysts to mediate synthetically relevant transformations that can be orthogonal, or akin to, native enzymatic reactivity. Peptide catalysts offer several useful features, such as modularity, ease of synthesis, and often enhanced compatibility with synthetic reaction conditions.In one intriguing area, our group has employed the proteinogenic amino acid aspartic acid (Asp) as a catalytic residue embedded within short peptide sequences to selectively introduce a singular oxygen atom into increasingly complex scaffolds, which might constitute a type of single atom editing. Our strategy has involved the development of an aspartic acid/peracid catalytic shuttle, a mechanism that, to our knowledge, has not yet been documented in enzymes.Our foray into Asp-catalyzed oxidation began with the discovery of a peptide sequence to impart enantioselectivity in the epoxidation of minimal olefins. This platform was then extended to include nucleophilic Baeyer-Villiger oxidations and electrophilic N- and S-atom oxidations. Of note, these reactions all use hydrogen peroxide as the stoichiometric oxidant; the appended peptide sequence dictates the selectivity on a per-reaction-type basis. Lead peptides for each transformation were identified using both combinatorial and rational design approaches, and mechanistic studies were used to guide our development along the way or to elucidate modes of action after the fact. In all cases, selectivity was achieved through critical noncovalent interactions between the substrate and peptide catalyst.We have always endeavored to test these catalysts in increasingly complex settings, facing difficult challenges in chemo-, site-, and stereoselectivity in a variety of molecular scaffolds. In a particularly forward-looking example, Asp-peptides were used to perform late-stage molecular editing of geldanamycin, a quintessentially complex and bioactive natural product. Asp-peptides have now also been used to edit the three-dimensional structure of loratadine, the active ingredient in Claritin, to generate helically chiral N-oxide analogues with chemo- and stereoselectivity. In the case of both geldanamycin and loratadine, the oxidized bioactive analogues underwent biological testing, providing insight into the development of future medicinally relevant molecules. Taken together, this Account details the power of Asp-catalysts to address challenges in asymmetric catalysis while also contributing to the need for rapid access to drug analogues.

Synthesis of chiral bicyclic proline analogs

2025-06-18

Radosław Gaida , Adam Włodarczyk , Marek Daszkiewicz +1 more | Tetrahedron

Avoiding the Hidden Costs of Peptide Synthesis: THIQ in DMI as an Alternative Fmoc-Deprotection Reagent

2025-06-18

Ming Chen , Fangxiang Sun , Gangqiang Yang | ACS Sustainable Chemistry & Engineering

Automated Iterative N‐C and C‐C Bond Formation

2025-06-18

Theodore Tyrikos‐Ergas , Sevasti Agiakloglou , Antonio J. LaPorte +7 more | Angewandte Chemie

Small molecule solutions to many contemporary societal challenges await discovery, but the artisanal and manual process via which this class of chemical matter is typically accessed limits the discovery of … Small molecule solutions to many contemporary societal challenges await discovery, but the artisanal and manual process via which this class of chemical matter is typically accessed limits the discovery of new functions. Automated assembly of (N‐methyl iminodiacetic acid) MIDA or (tetramethyl N‐methyl iminodiacetic acid) TIDA boronate building blocks via iterative C‐C bond formation, an approach we call “block chemistry”, alternatively enables generalized and automated preparation of many different types of small molecules in a modular fashion. But in its current form, this engine cannot also leverage nitrogen atoms as iteration handles. Here, we disclose a new iteration‐enabling group, CbzT, that reversibly attenuates the reactivity of nitrogen atoms and enables generalized catch‐and‐release purification. CbzT is leveraged to achieve the automated modular synthesis of Imatinib (Gleevec), an archetypical clinically approved kinase inhibitor, in which building blocks are iteratively linked by both N‐C and C‐C bonds. This work substantially expands the types of small molecules that can be iteratively assembled in an automated modular fashion. It also advances the concept of intentionally developing chemistry that machines can do.

Automated Iterative N‐C and C‐C Bond Formation

2025-06-18

Theodore Tyrikos‐Ergas , Sevasti Agiakloglou , Antonio J. LaPorte +7 more | Angewandte Chemie International Edition

A Scalable L‐α‐Glycerophosphorylcholine Synthesis through the Automatic pH‐Controlled (R)‐Glycidol Ring Opening with Phosphorylcholine

2025-06-17

António Massa , Mauro Anibaldi , Lorenzo de Ferra | Chemistry - Methods

The investigation of epoxide ring opening of ( R )‐glycidol with phosphorylcholine in water leads to the development of an effective synthesis of L‐α‐glycerophosphorylcholine (L‐α‐GPC), a commercially available drug. The … The investigation of epoxide ring opening of ( R )‐glycidol with phosphorylcholine in water leads to the development of an effective synthesis of L‐α‐glycerophosphorylcholine (L‐α‐GPC), a commercially available drug. The precise control of reaction pH with an automatic titrator proves to be crucial for achieving conversions of up to 98% and limiting byproduct formation. Additionally, an effective method for the synthesis of phosphocholine as inner salt is reported for the first time, which is also essential for achieving the described results.

Synthesis of oligomers with control of the monomer sequence and chirality

2025-06-16

| Nature Synthesis

On-DNA C–H functionalization of electron-rich arenes for DNA-encoded libraries

2025-06-16

Eduardo de Pedro Beato , Luca Torkowski , Philipp Hartmann +3 more | Nature Chemistry

Abstract DNA-encoded libraries (DELs) are useful for hit discovery in the pharmaceutical industry. Although a large number of individually coded molecules are accessible through DELs, their structural diversity is limited … Abstract DNA-encoded libraries (DELs) are useful for hit discovery in the pharmaceutical industry. Although a large number of individually coded molecules are accessible through DELs, their structural diversity is limited because few transformations are benign and chemoselective enough to be applied in the presence of DNA in aqueous environments. In particular, C–H functionalization chemistry that could be ideally suited to increase structural diversity through late-stage functionalization is currently absent from DEL synthesis. Here we present a general C–H functionalization of electron-rich arenes on DNA. The development of a selenoxide reagent is key to achieving the regio- and chemoselective formation of arylselenonium salts in aqueous media. The introduction of arylselenonium salts offers a versatile linchpin on DNA conjugates, which gives access to a multitude of analogues through diverse subsequent reactions, including transition-metal-mediated and photochemical transformations for the formation of C–C, C–I and C–S bonds.

Understanding the chemical stability of peptidomimetic therapeutics using high-resolution mass spectrometry: a study of terlipressin and its degradation products

2025-06-16

Ashwini Chawathe , Nitish Sharma | Analytical and Bioanalytical Chemistry

Designing Catalysts to Accelerate a Protein–Peptide Assembly-Reaction Cascade

2025-06-16

Yibin Sun , Yue Fang , Yajie Liu +4 more | ACS Central Science

Modular Synchronous Synthesis of Amides and α‐Ketoamides Realized by Matching Electrolysis‐Paired Tandems

2025-06-16

Qi‐Long Zhu , Qing Li , Dongdong Ma +6 more | Angewandte Chemie

Feasible electrolysis‐paired tandem synthesis represents an elaborately organized and high‐efficiency strategy balancing energy consumption and value‐added synthesis. Herein, we developed an exotic electrolysis‐paired tandem synthesis system driven by a metalloenzyme‐like … Feasible electrolysis‐paired tandem synthesis represents an elaborately organized and high‐efficiency strategy balancing energy consumption and value‐added synthesis. Herein, we developed an exotic electrolysis‐paired tandem synthesis system driven by a metalloenzyme‐like bifunctional single‐molecular heterostructure catalyst (MimNiPc/CNT), which enables the modular synchronous synthesis of amides and α‐ketoamides through cathodic CO‐relayed aminocarbonylation and anodic iodine‐mediated keto‐amidation tandem reactions, respectively. Notably, the established MimNiPc/CNT is not only effective for parallel electrolysis‐paired tandem reactions with various substrates, but also adaptable for both divergent and sequential electrolysis‐paired tandem reactions, producing value‐added amide and α‐ketoamide compounds with isolated yields up to ~90%. Detailed isotope labelling and mass spectrometry tracking experiments meticulously unveiled the reaction mechanisms, the processes at both electrodes can be refined into sequential electrocatalysis and chemocatalysis steps. Our work also demonstrates the flexibility and scalability of this "two birds with one stone" synthetic protocol, providing an experimental reference for precise synthesis.

Easy ROMP of Quinine Derivatives Toward Novel Chiral Polymers That Discriminate Mandelic Acid Enantiomers

2025-06-15

Mariusz Majchrzak , Karol Kacprzak , Marta Piętka +2 more | Polymers

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves … A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 104 – 2.26 × 104 g/mol and Mw = 2.90 × 104–3.05 × 104 g/mol with good polydispersity, ĐM = 1.32–1.35, and excellent thermal stability (up to 309°C Td10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain.

Drugs Based on Bioactive Oligopeptides

2025-06-15

Oleg V. Ledenev , O. V. Levitskaya , А. В. Сыроешкин | Journal of Drug Delivery and Therapeutics

Oligopeptides, i.e. biopolymers containing up to fifty amino acids, are being recognized as first-line treatments for a growing number of disorders. The review encompasses various aspects of the application of … Oligopeptides, i.e. biopolymers containing up to fifty amino acids, are being recognized as first-line treatments for a growing number of disorders. The review encompasses various aspects of the application of these active pharmaceutical ingredients, ranging from methods for obtaining a peptide molecule and formulating a dosage form, including excipients and their key properties, to various information on the pharmacokinetics and pharmacodynamics of peptide drugs supported by scientific experimental data, as well as modern quality control methods. The review considers that the application of peptide therapeutics covers a wide range of diseases. They include cancers of various genesis; bacterial infections; type 2 diabetes, neurological diseases, and eye diseases. The review notes that this is just a small fraction of the nosologies in which peptide bioregulators have demonstrated effective clinical activity. The review considers the role of excipients. A distinctive feature of the review is the consideration of innovative methods for quality control of peptide therapeutics. The methods include: high-performance liquid chromatography with tandem mass spectrometry, ultracentrifugation with flow-through rotors, dynamic laser light scattering, small-angle laser light scattering. The review specifically highlights the analysis of dispersion in turbid and opaque media – two-dimensional dynamic laser light scattering based on the kinetics of diffuse reflection with data analysis using a mathematical topological model. A non-invasive method for detecting intrinsic radiothermal emission of biologically active nanoparticles, which can be easily used for peptide molecules, is also described. The review presents a hypothesis according to which the background level of peptides forms a specific electromagnetic field of cells and tissues. Keywords: peptide drugs, modern drugs, safe drugs, peptide drugs review, peptide synthesis, peptide pharmacokinetics, peptide pharmacodynamics, drug excipients.

π‐Turns in Peptides: A Crystal‐State Literature Survey

2025-06-15

Barbara Biondi , Fernando Formaggio , Claudio Toniolo +2 more | Journal of Peptide Science

ABSTRACT The results of an analysis on the presence of π‐turns, characterized by an i ← i + 5 C=O···H–N intramolecular hydrogen bond, in the X‐ray diffraction structures of peptides … ABSTRACT The results of an analysis on the presence of π‐turns, characterized by an i ← i + 5 C=O···H–N intramolecular hydrogen bond, in the X‐ray diffraction structures of peptides are discussed. The survey returned a total of 55 π‐turn occurrences in linear and cyclic peptides. π‐Turns characterized by a helical conformation for residue i + 4, but with a screw sense opposite to that of the three preceding residues, are largely prevailing. They are often found at the C‐end of incipient or fully developed α‐helices, 3 10 ‐helices, and mixed α‐/3 10 ‐helices, thus acting as a C‐capping motif. However, the structures of two linear peptides and 15 cyclopeptides indicate that these types of π‐turns can exist in isolation, without the support of a preceding helix. The frequent presence of additional intramolecular hydrogen bonds internal to the π‐turn is also investigated. Cyclopeptides offered examples of two types of π‐turns that have no parallel in the structures of proteins. Differently from proteins, π‐turns characterized by helical ϕ, ψ sets of the same screw sense for all internal residues are hitherto unreported in the X‐ray diffraction structures of peptides. A suggestion for the rational design in peptides/peptidomimetics of a π‐turn featuring the screw‐sense reversal of residue i + 4 is proposed.

Design, Synthesis, and Application of Triazole-embedded Maltose-neopentyl-glycol (TMNG) Amphiphiles for Membrane Protein Studies

2025-06-14

Hongliang Cai , Xinyu Wu , Shixin Jin +4 more | Carbohydrate Research

Substrate‐Adapted Active Site Self‐Evolving Reconfiguration Boosting Catalytic Effect on Acetylene Semi‐Hydrogenation

2025-06-14

Zhong Zhang , Xujiao Ma , Danna Zhao +6 more | Angewandte Chemie International Edition

The facile synthesis of highly substrate‐adapted catalysts with dynamic active site adaptability remains a persistent challenge in heterogeneous catalysis. Herein, breaking through conventional catalyst preparation route of design–synthesis–evaluation iteration, we … The facile synthesis of highly substrate‐adapted catalysts with dynamic active site adaptability remains a persistent challenge in heterogeneous catalysis. Herein, breaking through conventional catalyst preparation route of design–synthesis–evaluation iteration, we demonstrate an active site self‐evolving reconfiguration strategy for spontaneous construction an adaptive multimolecular activation catalyst, such as for acetylene semi‐hydrogenation. Specifically, a metastable Cu single atom (Cu1) precursor as structural seed reconstructs to an exceptional acetylene semi‐hydrogenation catalyst under moderate operational conditions, which undergoes a copper active site reconfiguration employing reactants themselves as inducing medium. This self‐evolving reconfiguration creates cooperative Cu1 and Cu nanocluster (Cun) ensemble sites with a dynamic active configuration, which is unavailable by conventional thermal reduction methodology, for adaptive multi‐substrate H2 and acetylene activation. Hence, the resulting catalyst achieves full acetylene conversion with 96% ethylene selectivity and robust durability (>30 h) at a record‐low temperature of 120 °C, superior to reported copper‐based analogues. Such spontaneous active site self‐evolving reconfiguration offers a new possibility for intelligent catalyst engineering.

Substrate‐Adapted Active Site Self‐Evolving Reconfiguration Boosting Catalytic Effect on Acetylene Semi‐Hydrogenation

2025-06-14

Zhong Zhang , Xujiao Ma , Danna Zhao +6 more | Angewandte Chemie