Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands.

ABSTRACT: While a myriad non-coding RNAs are known to be essential in cellular processes and misregulated in diseases, the development of RNA-targeted small molecule probes has met with limited success. To elucidate the guiding principles for selective small molecule/RNA recognition, we analyzed cheminformatic and shape-based descriptors for 104 RNA-targeted ligands with demonstrated biological activity (RNA-targeted BIoactive ligaNd Database, R-BIND). We then compared R-BIND to both FDA-approved small molecule drugs and RNA ligands without reported bioactivity. Several striking trends emerged for bioactive RNA ligands, including: 1)?Compliance to medicinal chemistry rules, 2)?distinctive structural features, and 3)?enrichment in rod-like shapes over others. This work provides unique insights that directly facilitate the selection and synthesis of RNA-targeted libraries with the goal of efficiently identifying selective small molecule ligands for therapeutically relevant RNAs.

SUBMITTER: Morgan BS 

PROVIDER: S-EPMC5752130 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature