Evaluation of mismatch-binding ligands as inhibitors for Rev–RRE interaction

Drugs targeting the stem-loop IIB of Rev responsible element (RRE) of HIV-1 mRNA are potential therapeutic agents for HIV-1 infection. The stem loop is characterized by an internal loop consist of consecutive G-G and G-A mismatches, which is the single binding site for Rev protein for nuclear export of viral mRNA. We report here that ligands binding to G-G and G-A mismatches in duplex DNA also bind to the internal loop in competition with Rev peptide and lead to the dissociation of pre-formed Rev–RRE complex in a model system.

Mismatches in stem-loop IIB of RRE of HIV-1 are the site of Rev binding. Molecules binding to G-G and G-A mismatches in DNA were evaluated as inhibitors of RRE–Rev interaction.Figure optionsDownload as PowerPoint slide