Synthesis and analysis of substrate analogues for UDP-galactopyranose mutase: implication for an oxocarbenium ion intermediate in the catalytic mechanism.
[reaction: see text] UDP-D-galactofuranose (2), which is essential for both cell growth and virulence in many pathogenic microorganisms, is converted from UDP-D-galactopyranose (UDP-Galp, 1) by the flavin adenine dinucleotide (FAD)-dependent enzyme UDP-galactopyranose mutase (UGM). Here, we report the synthesis of UDP-GalOH (13) and show it as an inhibitor for UGM with a binding affinity similar to that of 1. These results are more consistent with a mechanism involving an oxocarbenium ion intermediate in UGM catalysis.
Itoh
Kenji
K
Division of Medicinal Chemistry, College of Pharmacy and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Huang
Zhishu
Z
Liu
Hung-wen
HW
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D007477:Ions / Q000737:chemistry*; D015394:Molecular Structure; D013379:Substrate Specificity
D007477:Ions; D019751:Intramolecular Transferases; C098051:UDP-galactopyranose mutase