Extended ethidium analogs as HIV-1 RRE binders

ORGN 130

Victor K Tam, vtam@chem.ucsd.edu, Qi Liu, qiliu@chem.ucsd.edu, and Yitzhak Tor, ytor@ucsd.edu. Department of Chemistry and Biochemistry, University of California, San Diego, MC 0358, 9500 Gilman Drive, La Jolla, CA 92093
The HIV Rev Response Element (RRE) is an RNA structure necessary for successful viral replication. Binding of the Rev protein to the RRE facilitates export of unspliced RNA out of the host nucleus, which is packaged into new viral particles as their primary genome. Small molecules that disrupt Rev protein and RRE binding are promising for anti-HIV agent development. Ethidium bromide is an intriguing molecule for drug development due to its high affinity for RNA. Despite being a promiscuous binder, selectivity for the RRE may be achieved by synthesizing larger-sized ethidium analogs targeted at the asymmetric bulge within the stem loop of the RRE. Selective intercalation in this portion of the viral genome may disrupt the Rev-RRE interaction. This poster will present our design, synthesis and evaluation of these extended ethidium analogs as a novel class of compounds for targeting specific structural motifs in HIV RNA.