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Structure-Guided Design of a Bioactive Covalent Small Molecule Targeting a Riboswitch

2025/10/07 by Chungen Li, Xueyi Yang, Kyle A. Dickerson +7 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Click Chemistry and Applications #Monoclonal and Polyclonal Antibodies Research #RNA and protein synthesis mechanisms

paper · pdf · doi:10.1021/jacs.5c13219

openalex publication_date 2025/10/07 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/15

Abstract

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.

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