A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics
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Author(s)
Walvoort, Maria Theresia Cornelia
Lukose, Vinita
Imperiali, Barbara
Date Issued
March 2016
Journal
Chemistry - A European Journal
Publisher
John Wiley & Sons, Inc.
Citation
Walvoort, Marthe T. C., Vinita Lukose, and Barbara Imperiali. “A Modular Approach to Phosphoglycosyltransferase Inhibitors Inspired by Nucleoside Antibiotics.” Chemistry - A European Journal 22, no. 11 (December 10, 2015): 3856-3864.
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Author's final manuscript
Abstract
Phosphoglycosyltransferases (PGTs) represent “gatekeeper” enzymes in complex glycan assembly pathways by catalyzing transfer of a phosphosugar from an activated nucleotide diphosphosugar to a membrane-resident polyprenol phosphate. The unique structures of selected nucleoside antibiotics, such as tunicamycin and mureidomycin A, which are known to inhibit comparable biochemical transformations, are exploited as the foundation for the development of modular synthetic inhibitors of PGTs. Herein we present the design, synthesis, and biochemical evaluation of two readily manipulatable modular scaffolds as inhibitors of monotopic bacterial PGTs. Selected compounds show IC[subscript 50] values down to the 40 μm range, thereby serving as lead compounds for future development of selective and effective inhibitors of diverse PGTs of biological and medicinal interest.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
http://dx.doi.org/10.1002/chem.201503986
