Bifunctional inhibition of HIV-1 reverse transcriptase: a first step in designing a bifunctional triphosphate.
Bioorg Med Chem Lett
; 23(5): 1511-8, 2013 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23380374
ABSTRACT
The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker. A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Inibidores da Transcriptase Reversa
/
Transcriptase Reversa do HIV
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos