Identification of a Selective Small-Molecule Ligand for HIV-1 Frameshift-Inducing Stem-Loop RNA from an 11,325 Member Resin Bound Dynamic Combinatorial Library

Molecules capable of binding a specific RNA sequence with high affinity and selectivity can serve as valuable tools for modulating RNA-dependent cellular events. In this communication, we describe the synthesis and evaluation of an 11,325 member dynamic combinatorial library, the largest prepared to date, that targets an RNA stem-loop critical to HIV proliferation. From this library, a molecule was identified that binds this RNA with high affinity and selectivity.