Structure-Activity Relationship of Flavin Analogues That Target the Flavin Mononucleotide Riboswitch.

ABSTRACT: The flavin mononucleotide (FMN) riboswitch is an emerging target for the development of novel RNA-targeting antibiotics. We previously discovered an FMN derivative, 5FDQD, that protects mice against diarrhea-causing Clostridium difficile bacteria. Here, we present the structure-based drug design strategy that led to the discovery of this fluoro-phenyl derivative with antibacterial properties. This approach involved the following stages: (1) structural analysis of all available free and bound FMN riboswitch structures; (2) design, synthesis, and purification of derivatives; (3) in vitro testing for productive binding using two chemical probing methods; (4) in vitro transcription termination assays; and (5) resolution of the crystal structures of the FMN riboswitch in complex with the most m

SUBMITTER: Vicens Q 

PROVIDER: S-EPMC6874366 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature