Single atom changes in newly synthesized HIV protease inhibitors reveal structural basis for extreme affinity, high genetic barrier, and adaptation to the HIV protease plasticity.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
30 06 2020
30 06 2020
Historique:
received:
26
09
2019
accepted:
15
04
2020
entrez:
2
7
2020
pubmed:
2
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
HIV-1 protease inhibitors (PIs), such as darunavir (DRV), are the key component of antiretroviral therapy. However, HIV-1 often acquires resistance to PIs. Here, seven novel PIs were synthesized, by introducing single atom changes such as an exchange of a sulfur to an oxygen, scission of a single bond in P2'-cyclopropylaminobenzothiazole (or -oxazole), and/or P1-benzene ring with fluorine scan of mono- or bis-fluorine atoms around DRV's scaffold. X-ray structural analyses of the PIs complexed with wild-type Protease (PR
Identifiants
pubmed: 32606378
doi: 10.1038/s41598-020-65993-z
pii: 10.1038/s41598-020-65993-z
pmc: PMC7326966
doi:
Substances chimiques
HIV Protease Inhibitors
0
HIV Protease
EC 3.4.23.-
Darunavir
YO603Y8113
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10664Subventions
Organisme : NIAID NIH HHS
ID : R37 AI150466
Pays : United States
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