THE BINDING MODE OF DRUGS TO THE TAR RNA OF HIV-1 STUDIED BY ELECTRICLINEAR DICHROISM

For the first time, the interaction between a series of small molecule s and the TAR RNA of HIV-1 has been investigated by electric linear di chroism (ELD). The compounds tested include the DNA intercalating drug s proflavine and ethidium bromide and an amsacrine-4-carboxamide DNA-t hreading intercalator as well as the AT-specific DNA minor groove bind ers netropsin, Hoechst 33258, berenil and DARI. In all cases except fo r netropsin, negative reduced dichroism signals were measured in the d rug absorption band. in agreement with previous studies, the results i ndicate that both classical and threading intercalation can occur with the TAR RNA, The ELD data show that the mode of binding of the drugs Hoechst 33258, berenil and DAPI to the TAR RNA is similar to their bin ding mode in GC-rich regions of DNA and likely involves intercalation into the A-form TAR RNA helix. The wide and shallow minor groove of th e TAR RNA is apparently not accessible to DNA minor groove binding dru gs such as netropsin. The ELD technique appears uniquely valuable as a means of investigating the interaction of drugs with the TAR RNA.