Inhibition of HIV-1 replication by a Tat RNA-binding domain peptide analog

The peptidic compound, N-acetly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Cys(biotin)-NH2 (Tat10-biotin), contains-the 9-amino acid sequence from the basic domain or the Tat protein responsible for specific interaction with TAR RNA. The cysteine residue provides an attachment site for biotin, which acts as a cellular uptake enhancer. Tat10-biotin binds a fragment of TAR RNA (Delta TAR) avidly and specifically, as measured in an electrophoretic gel shift assay. Tat10-biotin inhibited tar gene-induced expression of a stably transfected chloramphenicol acetyl transferase (CAT) reporter gene linked to the HIV-1 long terminal repeat (LTR) in a model cell assay, but did riot inhibit phorbol ester-induced expression of CAT, thereby demonstrating a Tat-dependent mechanism of inhibition, Inhibition of HIV-I replication after acute infection of MT2 cells was demonstrated by absence of HN-induced syncytium formation and cytotoxicity, as well as by suppression of reverse transcriptase production. These results suggest that a peptide or peptide mimetic capable of competing with the TAR RNA-binding domain of Tar protein might be useful as a therapeutic agent for AIDS.