Nitrile-based peptoids as cysteine protease inhibitors.

Cysteine Proteinase Inhibitors / chemistry Models, Molecular Molecular Docking Simulation Molecular Structure Nitriles / chemistry Peptides / chemistry
Biochemical kinetic assays Cysteine protease inhibitors Docking Nitrile warhead Peptoids

Journal

Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298

Informations de publication

Date de publication:
01 07 2021
Historique:
received: 21 01 2021
revised: 28 04 2021
accepted: 30 04 2021
pubmed: 16 5 2021
medline: 9 11 2021
entrez: 15 5 2021
Statut: ppublish

Résumé

Peptidomimetics of the class of dipeptidyl nitrile analog peptoids were synthesized as inhibitors of mammalian cysteine proteases of the papain superfamily. The dipeptidyl nitrile side chains were attached to the peptide backbone's nitrogen atom, not to the α-carbons. Synthesized nitrile-based peptoid analogs that lack the hydrogen amide at P2-P3 are responsible for many of the secondary structure elements in peptides and proteins, making them resistant to proteolysis. The designed peptoids would lose a hydrogen bond with cruzain Asp161 decreasing the affinity toward the enzyme. A structure-activity relationship and matched molecular pair-based analysis between the dipeptidyl nitrile Neq0409 and its peptoid 4a yielded the following cruzain affinities: pK

Identifiants

DOI: 10.1016/j.bmc.2021.116211 PMID: 33991733
pubmed: 33991733
pii: S0968-0896(21)00219-4
doi: 10.1016/j.bmc.2021.116211
pii:
doi:

Substances chimiques

Cysteine Proteinase Inhibitors 0
Nitriles 0
Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

116211

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Luana Alves (L)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil.

Deborah A Santos (DA)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil. Electronic address: deborah.araujo89@gmail.com.

Rodrigo Cendron (R)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil.

Fernanda R Rocho (FR)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil.

Thiago K B Matos (TKB)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil.

Andrei Leitão (A)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil. Electronic address: andleitao@iqsc.usp.br.

Carlos A Montanari (CA)

Medicinal and Biological Chemistry Group (NEQUIMED), Institute of Chemistry of São Carlos, University of São Paulo, São Carlos/SP, Brazil.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Inhibiteurs de la cystéine protéinase › Nitrile-based peptoids as cysteine protease inhibitors.
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Nitrile-based peptoids as cysteine protease inhibitors.
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de docking moléculaire › Nitrile-based peptoids as cysteine protease inhibitors.
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Nitrile-based peptoids as cysteine protease inhibitors.
questionsmedicales.fr › Composés chimiques organiques › Nitriles › Nitrile-based peptoids as cysteine protease inhibitors.
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Nitrile-based peptoids as cysteine protease inhibitors.