Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases.
Aldehydes
/ chemistry
Cathepsin L
/ antagonists & inhibitors
Chagas Disease
/ drug therapy
Cysteine Endopeptidases
/ metabolism
Cysteine Proteases
/ metabolism
Cysteine Proteinase Inhibitors
/ chemistry
Drug Design
Humans
Kinetics
Models, Molecular
Molecular Structure
Protozoan Proteins
/ antagonists & inhibitors
SARS-CoV-2
/ drug effects
Structure-Activity Relationship
Trypanosoma cruzi
/ drug effects
COVID-19 Drug Treatment
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
12 08 2021
12 08 2021
Historique:
pubmed:
22
7
2021
medline:
19
8
2021
entrez:
21
7
2021
Statut:
ppublish
Résumé
Cysteine proteases comprise an important class of drug targets, especially for infectious diseases such as Chagas disease (cruzain) and COVID-19 (3CL protease, cathepsin L). Peptide aldehydes have proven to be potent inhibitors for all of these proteases. However, the intrinsic, high electrophilicity of the aldehyde group is associated with safety concerns and metabolic instability, limiting the use of aldehyde inhibitors as drugs. We have developed a novel class of self-masked aldehyde inhibitors (SMAIs) for cruzain, the major cysteine protease of the causative agent of Chagas disease-
Identifiants
pubmed: 34288674
doi: 10.1021/acs.jmedchem.1c00628
pmc: PMC10504874
mid: NIHMS1914999
doi:
Substances chimiques
Aldehydes
0
Cysteine Proteinase Inhibitors
0
Protozoan Proteins
0
Cysteine Proteases
EC 3.4.-
Cysteine Endopeptidases
EC 3.4.22.-
Cathepsin L
EC 3.4.22.15
cruzipain
EC 3.4.22.51
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11267-11287Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM129076
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127634
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI166624
Pays : United States
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