INHIBITION OF HIV-1 REPLICATION USING OLIGOCARBAMATE DERIVATIVES

摘要

Tat-inhibitory oligocarbamate derivatives of the formula I (see formula I) and analogs thereof, and the biologically and pharmaceutically acceptable salts thereof exhibit advantageous properties, including specific binding to TAR RNA with high affinities, and stability of the resultant oligocarbamate-RNA complexes to proteolytic digestion. Site-specific photocrosslinking experiments using a photoactive analog (4- thio-uracil) containing TAR RNA indicate that these oligocarbamates interact with RNA in the major groove. These oligocarbamates are thus capable of competing with the TAR RNA-binding domain of Tat protein and thus are useful as a therapeut ic agents in the treatment of AIDS.