期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 56, 期 43, 页码 13498-13502出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201707641
关键词
chemical probes; cheminformatics; molecular recognition; principal moments of inertia; RNA recognition
资金
- Duke University
- US National Institute of Health [P50GM103297]
- Prostate Cancer Foundation Young Investigator Award
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.
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