Journal ArticleDOI
Cyclic peptides with a phosphinic bond as potent inhibitors of a zinc bacterial collagenase.
Athanasios Yiotakis,Alain Lecoq,Stamatia Vassiliou,Isabelle Raynal,Philippe Cuniasse,Vincent Dive +5 more
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TLDR
Interestingly, the kinetic analysis for the binding of the cyclic peptide inhibitors Ia and Va to the collagenase, as compared to a linear parent compound, reveals that the lower potency of the Cyclic peptides is mostly the consequence of a lower rate constant for association to the enzyme.Abstract:
A series of cyclic peptides containing a phosphinic bond were synthesized and evaluated as inhibitors of a zinc bacterial collagenase from Corynebacterium rathaii. Among this series of pseudopeptides of different sizes of cycles, only two molecules Ia (cyclo[Gly-Pro-Phe psi(PO2CH2)-Gly-Pro-Ahx]) and Va (cyclo[beta Ala-Pro-Phe psi (PO2CH2)Gly-Pro-Ahx]) were found to be rather potent inhibitors of this protease, with Ki values of 120 and 90 nM, respectively. Besides the influence of the peptide ring size, this study suggests that both the stereochemical and the conformational properties of the pseudophenylalanine residue in these cyclic peptides may determine their potency. Interestingly, the kinetic analysis for the binding of the cyclic peptide inhibitors Ia and Va to the collagenase, as compared to a linear parent compound, reveals that the lower potency of the cyclic peptides is mostly the consequence of a lower rate constant for association to the enzyme. To our knowledge, this is the first report on cyclic phosphinic peptides and on their activities as inhibitors of a zinc protease.read more
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Selected organophosphorus compounds with biological activity. Applications in medicine
TL;DR: An overview of the latest applications of organophosphorus compounds (OPs) that exhibit biological activity can be found in this article, where the authors outline the findings of a literature review on OPs, including anticancer and antiviral agents, bisphosphonates, phosphorus analogues of amino acids and peptides.
Journal ArticleDOI
Development of Highly Potent and Selective Phosphinic Peptide Inhibitors of Zinc Endopeptidase 24-15 Using Combinatorial Chemistry
Jiri Jiracek,Athanasios Yiotakis,Bruno Vincent,Alain Lecoq,Anna Nicolaou,Frédéric Checler,Vincent Dive +6 more
TL;DR: This study demonstrates that the combinatorial chemistry approach leading to the development of phosphinic peptide libraries is a powerful strategy for discovering highly potent and selective inhibitors of zinc metalloproteases and should find a broader application in studies of this important class of enzymes.
Journal ArticleDOI
Development of the First Potent and Selective Inhibitor of the Zinc Endopeptidase Neurolysin Using a Systematic Approach Based on Combinatorial Chemistry of Phosphinic Peptides
TL;DR: The efficiency of this novel approach in rapid identification of the first potent inhibitor of the mammalian zinc endopeptidase neurolysin (24-16) is demonstrated, able to discriminate between this enzyme and the related zinc endopesetidase thimet oligopePTidase ( 24-15).
Journal ArticleDOI
Phosphinic peptides as zinc metalloproteinase inhibitors.
Vincent Dive,Dimitris Georgiadis,Magdalini Matziari,A. Makaritis,Fabrice Beau,Philippe Cuniasse,Athanasios Yiotakis +6 more
TL;DR: Specific properties of the inhibitors produced in recent years are reviewed, supporting the notion that phosphinic pseudo-peptides are useful tools for studying the structural and functional biology of zinc proteases.
Journal ArticleDOI
Multistep tandem mass spectrometry for Sequencing Cyclic Peptides in an Ion-Trap Mass Spectrometer
TL;DR: The power of the strategy lies in the capability to execute several stages of CAD upon a precursor ion and its decomposition products, allowing the cyclic peptide to be sequenced in an unambiguous, stepwise manner.
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