Abstract
The DNA x RNA hybrid duplexes are functionally important structures in gene expression that are underutilized as potential drug targets. Several tools are described here for the discovery and characterization of small molecules capable of the selective recognition of DNA x RNA hybrid structures. Competition dialysis and thermal denaturation of mixtures of polynucleotide structures can be used to identify small molecules that bind selectively to DNA x RNA hybrids. An assay that measures small molecule inhibition of RNase H can be used to measure a functional response to these ligands.