Mechanism-based candidate inhibitors of uridine diphosphate galactopyranose mutase (UGM)

No Thumbnail Available
File version
Author(s)
Mahdavi-Amiri, Y
Mohan, S
Borrelli, S
Slowski, K
Sanders, DAR
Pinto, BM
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2016
Size
File type(s)
Location
License
Abstract

Uridine diphosphate-galactopyranose mutase (UGM), an enzyme found in many eukaryotic and prokaryotic human pathogens, catalyzes the interconversion of UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf), the latter being used as the biosynthetic precursor of the galactofuranose polymer portion of the mycobacterium cell wall. We report here the synthesis of a sulfonium and selenonium ion with an appended polyhydroxylated side chain. These compounds were designed as transition state mimics of the UGM-catalyzed reaction, where the head groups carrying a permanent positive charge were designed to mimic both the shape and positive charge of the proposed galactopyranosyl cation-like transition state. An HPLC-based UGM inhibition assay indicated that the compounds inhibited about 25% of UGM activity at 500 μM concentration.

Journal Title
Carbohydrate Research
Conference Title
Book Title
Edition
Volume
419
Issue
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Biochemistry and cell biology
Enzyme inhibitors
Mycobacterium tuberculosis
Synthesis
Transition-state analogues
UDP-galactopyranose mutase
Persistent link to this record
Citation
Mahdavi-Amiri, Y; Mohan, S; Borrelli, S; Slowski, K; Sanders, DAR; Pinto, BM, Mechanism-based candidate inhibitors of uridine diphosphate galactopyranose mutase (UGM), Carbohydrate Research, 2016, 419, pp. 1-7
Collections