2'-ß-Methylselenyl nucleos(t)ide analogs as reverse transcriptase inhibitors against diverse HIV mutants.
Bioorg Med Chem
; 110: 117813, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-38954919
ABSTRACT
Nucleoside reverse transcriptase inhibitors (NRTIs) have been extensively studied as drugs targeting HIV RT. However, the practice or use of approved NRTIs lacking the 3'-hydroxy group often promotes frequent HIV mutations and generates drug-resistance. Here, we describe a novel NRTI with 2'-ß-methylselenyl modification. We found that this modification inhibited the DNA elongation reaction by HIV-1 RT despite having a 3'-hydroxy group. Moreover, the conformation of this nucleoside analog is controlled at C3'-endo, a conformation that resists excision from the elongating DNA by HIV RT. Accordingly, the designed analogs exhibited activity against both wild-type HIV and multidrug-resistant HIV mutants.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
HIV-1
/
Inibidores da Transcriptase Reversa
/
Fármacos Anti-HIV
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Transcriptase Reversa do HIV
/
Mutação
Limite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
/
Bioorg. med. chem
/
Bioorganic & medicinal chemistry
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Japão