Molecular basis of HIV-1 TAR RNA specific recognition by an acridine tat-antagonist

被引：31

作者：

Gelus, N

Hamy, F

Bailly, C

机构：

[1] IRCL, INSERM U524, F-59045 Lille, France

[2] Novartis Pharma Inc, Pharma Res, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 06期

关键词：

TAR RNA; antiviral drugs; acridine; HIV-1;

D O I：

10.1016/S0968-0896(99)00030-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We investigated the interaction of a highly potent acridine-based tar-antagonist with the TAR RNA of HIV-1. The wild type TAR RNA and three mutants with U-->C23, G . C-->C . G26-39 or G . C-->A . 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 . 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. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1075 / 1079

页数：5

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