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.