Chungen Li, Xueyi Yang, Kyle A. Dickerson, Patrick R. A. Zanon, Noah A. Springer, Jielei Wang, Yilin Jia, Nikhil C. Munshi, Robert Batey, Matthew D. Disney
Small molecule ligands targeting structured RNA elements hold promise for modulating RNA function, serving as chemical probes and potential therapeutics. In this study, the characterization of phenylglyoxal-based covalent probe designed to target unpaired guanine residues in structured RNAs is reported. A structure-guided design strategy was employed to modify covalently unpaired guanines critical for flavin mononucleotide (FMN) binding to the FMN riboswitch. Covalent modification occurs at the designed site and modulates riboswitch function in a cellular reporter system, highlighting the potential of covalent mechanisms of action for bioactive RNA ligands.