INHIBITION OF AN HIV-1 TAT-DERIVED PEPTIDE BINDING TO TAR RNA BY AMINOGLYCOSIDE ANTIBIOTICS

Aminoglycoside antibiotics were found for the first time to inhibit an HIV-1 Tat-derived peptide binding to TAR RNA. The IC50 values of neom ycin, streptomycin, and gentamicin were determined as 0.92 mu M, 9.5 m u M, and 45 mu M, respectively. In the absence of Tat peptide these an tibiotics were found to cause mobility shifts of the TAR RNA on non-de naturing polyacrylamide gels. This is the first example, to our knowle dge, of non-peptide or non-nucleotide like small molecules that bind t o and induce a mobility shift of TAR RNA. It was further found that th e antibiotics which demonstrate higher affinity for TAR are better inh ibitors of the Tat/TAR interaction. Mutational and competition studies indicate that neomycin binds to the duplex domain of TAR RNA.