Application of an NMR/Crystallography Fragment Screening Platform for the Assessment and Rapid Discovery of New HIV-CA Binding Fragments.
ChemMedChem
; 19(13): e202400025, 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38581280
ABSTRACT
Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have 19F-pKi values of 5.3 and 5.4 respectively.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fármacos Anti-HIV
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article