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 neomycin, streptomycin, and gentamicin were determined as 0.92 μM, 9.5 μM, and 45 μM, respectively. In the absence of Tat peptide these antibiotics were found to cause mobility shifts of the TAR RNA on non-denaturing polyacrylamide gels. This is the first example, to our knowledge, of non-peptide or non-nucleotide like small molecules that bind to and induce a mobility shift of TAR RNA. It was further found that the antibiotics which demonstrate higher affinity for TAR are better inhibitors of the Tat/TAR interaction. Mutational and competition studies indicate that neomycin binds to the duplex domain of TAR RNA.