Identification of inhibitors of UDP-galactopyranose mutase via combinatorial in situ screening. Issue 8 (10th February 2021)

• Record Type: Journal Article
• Authors: Fu, Jian; Fu, Huixiao; Xia, Yufen; N'Go, Inès; Cao, Jun; Pan, Weidong; Vincent, Stéphane P.
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 8(2021)
• Page Start: 1818
• Page End: 1826
• Publication Date: 2021-02-10
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00138h
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : An in situ screening assay for UDP-galactopyranose mutase (UGM, an essential enzyme of M. tuberculosis cell wall biosynthesis) has been developed to discover novel UGM inhibitors. Abstract : An in situ screening assay for UDP-galactopyranose mutase (UGM, an essential enzyme of M. tuberculosis cell wall biosynthesis) has been developed to discover novel UGM inhibitors. The approach is based on the amide-forming reaction of an amino acid core with various cinnamic acids, followed by a direct fluorescence polarization assay to identify the best UGM binders without isolation and purification of the screened ligands. This assay allows us to perform one-pot high-throughput synthesis and screening of enzyme inhibitors in a 384-well plate format. UGM ligands were successfully identified by this technology and their inhibition levels were established from pure synthetic compounds in vitro and in a whole cell antibacterial assay. This study provides a blueprint for designing enamide structures as new UGM inhibitors and anti-mycobacterial agents.