The identification of RNA-privileged scaffolds and chemical space has the ability to dramatically expedite the identification of selective chemical probes targeted toward a number of disease-related RNAs. We elucidated this space by identifying small molecules reported in the literature to have promising biological activity against non-ribosomal RNA targets and compared their physicochemical, structural and spatial properties to those of protein-targeted bioactive ligands (i.e. FDA drugs). While the bioactive RNA ligands were found not to violate traditional medicinal chemistry rules, the analysis delineated clear differences in structural and spatial properties between RNA- and protein-targeted chemical probes. These properties have been applied to a variety of chemical scaffolds and RNA targets, revealing a promising strategy to rationally design and select RNA-biased small molecules.

Discovery and application of cheminformatics-derived principles for small molecule:RNA targeting

255th National Meeting (2018)

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