Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands.
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.
Duke Scholars
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Related Subject Headings
- Small Molecule Libraries
- RNA
- Principal Component Analysis
- Organic Chemistry
- Ligands
- Drug Discovery
- Databases, Chemical
- 34 Chemical sciences
- 03 Chemical Sciences
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Small Molecule Libraries
- RNA
- Principal Component Analysis
- Organic Chemistry
- Ligands
- Drug Discovery
- Databases, Chemical
- 34 Chemical sciences
- 03 Chemical Sciences