Inhibition of Galactosyltransferases by a Novel Class of Donor Analogues

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DOIResolve DOI: http://doi.org/10.1021/jm201154p
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TypeArticle
Journal titleJournal of Medicinal Chemistry
ISSN0022-2623
1520-4804
Volume55
Issue5
Pages20152024; # of pages: 10
AbstractGalactosyltransferases (GalT) are important molecular targets in a range of therapeutic areas, including infection, inflammation, and cancer. GalT inhibitors are therefore sought after as potential lead compounds for drug discovery. We have recently discovered a new class of GalT inhibitors with a novel mode of action. In this publication, we describe a series of analogues which provide insights, for the first time, into SAR for this new mode of GalT inhibition. We also report that a new C-glycoside, designed as a chemically stable analogue of the most potent inhibitor in this series, retains inhibitory activity against a panel of GalTs. Initial results from cellular studies suggest that despite their polarity, these sugar-nucleotides are taken up by HL-60 cells. Results from molecular modeling studies with a representative bacterial GalT provide a rationale for the differences in bioactivity observed in this series. These findings may provide a blueprint for the rational development of new GalT inhibitors with improved potency.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number21269036
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Record identifier06099a81-e608-4cc7-a79c-8eb40729c0f5
Record created2013-12-02
Record modified2016-05-09
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