Abstract: This invention relates to the use of oligourea molecules to specifically inhibit protein-nucleic acid interactions. In particular, it provides an oligourea molecule that competes with the Tat molecule for the TAR RNA of HIV-1. Also provided is a method specifically inhibiting protein-nucleic and interactions, and kits.

Abstract: The Tat-inhibitory polypeptide derivatives of the formula I D-Cys-D-Phe-D-Thr-D-Thr-D-Lys-D-Ala-D-Leu-D-Gly-D-Ile-D-Ser-D-Tyr-D-Gly-D-Arg-D-Lys-D-Lys-D-Arg-D-Arg-D-Gln-D-Arg-D-Arg-D-Arg-D-Pro-D-Pro-D-Gln-D-Gly-D-Ser-D-Gln-D-Thr-D-His-D-Gln-D-Val-D-Ser-D-Leu-D-Ser-D-Lys-D-Gln (SEQ ID 1) and fragments or analogs thereof, and the biologically and pharmaceutically acceptable salts thereof exhibit advantageous properties, including binding to &Dgr;TAR, inhibition of LTR-dependent reporter gene expression in a model cell assay and, finally, inhibition of HIV-1 replication, as determined in assays of HIV-induced syncytium formation, cytotoxicity and reverse transcriptase production. These peptides are thus capable of competing with the TAR RNA-binding domain of Tat protein and thus are useful as a therapeutic agents in the treatment of AIDS.

Abstract: Tat-inhibitory oligocarbamate derivatives of the formula I ##STR1## 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 therapeutic agents in the treatment of AIDS.