Inhibition of escherichia coli glycosyltransferase MurG and mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimics
Trunkfield, Amy E., Gurcha, Sudagar S., Besra, Gurdyal S. and Bugg, Tim. (2010) Inhibition of escherichia coli glycosyltransferase MurG and mycobacterium tuberculosis Gal transferase by uridine-linked transition state mimics. Bioorganic & Medicinal Chemistry, Vol.18 (No.7). pp. 2651-2663. ISSN 0968-0896Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bmc.2010.02.026
Glycosyltransferase MurG catalyses the transfer of N-acetyl-D-glucosamine to lipid intermediate I on the bacterial peptidoglycan biosynthesis pathway, and is a target for development of new antibacterial agents. A transition state mimic was designed for MurG, containing a functionalised proline, linked through the alpha-carboxylic acid, via a spacer, to a uridine nucleoside. A set of 15 functionalised prolines were synthesised, using a convergent dipolar cycloaddition reaction, which were coupled via either a glycine, proline, sarcosine, or diester linkage to the 5'-position of uridine. The library of 18 final compounds were tested as inhibitors of Escherichia coli glycosyltransferase MurG. Ten compounds showed inhibition of MurG at 1 mM concentration, the most active with IC50 400 mu M. The library was also tested against Mycobacterium tuberculosis galactosyltransferase GlfT2, and one compound showed effective inhibition at 1 mM concentration. (C) 2010 Elsevier Ltd. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
Q Science > QR Microbiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Glycosyltransferases, Peptidoglycans -- Synthesis, Enzyme inhibitors, Mycobacterium tuberculosis, Escherichia coli|
|Journal or Publication Title:||Bioorganic & Medicinal Chemistry|
|Official Date:||April 2010|
|Number of Pages:||13|
|Page Range:||pp. 2651-2663|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Royal Society (Great Britain), Engineering and Physical Sciences Research Council (EPSRC), University of Warwick, Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England)|
|Grant number:||081569/Z/06/Z (WT)|
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