Human cytomegalovirus; antiviral; indolocarbazoles; protein kinase C; inhibitors

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.