Dynamic combinatorial chemistry as a rapid method for discovering sequence-selective RNA-binding compounds.

The ever-growing number of RNA species that are recognized as having a role in human disease is driving a demand for novel molecular probes and therapeutics. Producing sequence-selective RNA-binding molecules remains a substantial challenge, however. One approach that has been successful in producing molecules with high affinity and specificity for disease-relevant RNAs is the use of dynamic combinatorial chemistry, a fragment-based method in which fragments combine reversibly in the presence of the target. We describe methods for the design, synthesis, and screening of dynamic combinatorial libraries targeting RNA.