title: Synthesis and Evaluation of Bicyclo[3.1.0]hexane-Based UDP-Galf Analogues as Inhibitors of the Mycobacterial Galactofuranosyltransferase GlfT2.
abstract: UDP-galactofuranose (UDP-Galf) is the donor substrate for both bifunctional galactofuranosyltransferases, GlfT1 and GlfT2, which are involved in the biosynthesis of mycobacterial galactan. In this paper, a group of UDP-Galf mimics were synthesized via reductive amination of a bicyclo[3.1.0]hexane-based amine by reacting with aromatic, linear, or uridine-containing aldehydes. These compounds were evaluated against GlfT2 using a coupled spectrophotometric assay, and were shown to be weak inhibitors of the enzyme.
authors.affiliation: Department of Chemistry and Alberta Glycomics Centre, University of Alberta, 11227 Saskatchewan Drive, Edmonton, AB T6G2G2, Canada. tlowary@ualberta.ca.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Lowary
authors.affiliation: College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163319, Heilongjiang Province, China. lijingroea@sina.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006586:Hexanes / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009161:Mycobacterium / Q000187:drug effects / Q000201:enzymology*; D014530:Uridine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D006586:Hexanes; C104136:uridine diphosphate galactofuranose; D014530:Uridine Diphosphate; D005690:Galactose
keywords: UDP-Galf; galactofuranosyltransferases; inhibitors; mycobacteria; reductive amination; tuberculosis