Molecular basis of HIV-1 TAR RNA specific recognition by an acridine tat-antagonist.
1999
Abstract 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·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.
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