Publications [#328434] of Amanda Hargrove

Journal Articles

1. Morgan, BS; Forte, JE; Culver, RN; Zhang, Y; Hargrove, AE, Discovery of Key Physicochemical, Structural, and Spatial Properties of RNA-Targeted Bioactive Ligands., Angewandte Chemie (International ed. in English), vol. 56 no. 43 (October, 2017), pp. 13498-13502, Wiley [doi]
   (last updated on 2024/12/31)

   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.