Nucleotide Sugar Pucker Preference Mitigates Excision by HIV-1 RT.
ACS Chem Biol
; 10(9): 2024-33, 2015 Sep 18.
Article
en En
| MEDLINE
| ID: mdl-26131619
ABSTRACT
A series of DNA primers containing nucleotides with various sugar pucker conformations at the 3'-terminus were chemically synthesized by solid-phase synthesis. The ability of wild-type (WT) HIV-1 reverse transcriptase (RT) and AZT-resistant (AZTr) RT to excise the 3'-terminal nucleotide was assessed. Nucleosides with a preference for the North conformation were more refractory to excision by both WT-RT and AZTr-RT. We found that DNA primers that contain North puckered-nucleotides at the 3'-terminus can also affect the translocation status of the RT/template/primer complex, which provides an underlying mechanism to avoid being excised. Together, these results point to a correlation between the sugar conformation of the 3'-terminal nucleotide, the precise position of HIV-1 RT on its nucleic acid substrate, and, in turn, its catalytic function. Nucleotide sugar conformation is therefore an important parameter in defining the susceptibility to RT-catalyzed phosphorolytic excision.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
VIH-1
/
Fármacos Anti-VIH
/
Transcriptasa Inversa del VIH
/
Nucleósidos
Límite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá