Molecular basis of HIV-1 TAR RNA specific recognition by an acridine tat-antagonist.
We investigated the interaction of a highly potent acridine-based tat-antagonist with the TAR RNA of HIV-1. The wild type TAR RNA and three mutants with U-->C23, G x C-->C x G26-39 or G x C-->A x U26-39 substitutions were used as substrates to study the molecular basis of drug-TAR RNA complex formation. Melting temperature and RNase protection experiments reveal that the G x C26-39 pair is a critical element for specific major groove recognition of TAR at the pyrimidine bulge. The results provide a rational basis for future design of optimized tat/TAR inhibitors.
Gelus
N
N
INSERM Unité 524, IRCL, Lille, France.
Hamy
F
F
Bailly
C
C
D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D018983:DNA Footprinting; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation; D012367:RNA, Viral / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus
D000166:Acridines; D019380:Anti-HIV Agents; C120944:CPG 40336A; D015696:Gene Products, tat; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus