Document Report Card

ID: ALA2069297

Journal: J Med Chem

Title: Inhibition of galactosyltransferases by a novel class of donor analogues.

Authors: Descroix K, Pesnot T, Yoshimura Y, Gehrke SS, Wakarchuk W, Palcic MM, Wagner GK.

Abstract: Galactosyltransferases (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.

CiteXplore: 22356319

DOI: 10.1021/jm201154p