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

Journal Article

While 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 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, RBIND). 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: i) compliance to medicinal chemistry rules; ii) distinctive structural features; and iii) enrichment in "rod-like" over other shapes. 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.

Full Text

Duke Authors

Cited Authors

  • Morgan, BS; Forte, JE; Culver, RN; Zhang, Y; Hargrove, AE

Published Date

  • August 15, 2017

Published In

PubMed ID

  • 28810078

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

International Standard Serial Number (ISSN)

  • 1433-7851

Digital Object Identifier (DOI)

  • 10.1002/anie.201707641


  • eng