Design of Glycosyltransferase Inhibitors: Serine Analogues as Pyrophosphate Surrogates?. Issue 10 (14th July 2015)

• Record Type: Journal Article
• Authors: Wang, Shuai; Cuesta‐Seijo, Jose A.; Striebeck, Alexander; Lafont, Dominique; Palcic, Monica M.; Vidal, Sébastien
• Is Part Of: ChemPlusChem. Volume 80:Issue 10(2015:Oct.)
• Page Start: 1525
• Page End: 1532
• Publication Date: 2015-07-14
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201500282
• Languages: English
• ISSNs: 2192-6506

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Mimicking the diphosphate moiety of nucleotide diphosphate sugars with serine analogues provided modest glycosyltransferase inhibitors. The synthetic strategy employed a combination of glycosylation, amide bond formation and azide–alkyne "click" chemistry. Inhibition constants (<italic>K</italic>_i) in the high micromolar range were obtained with a selection of five galactosyltransferases. Cocrystals of three inhibitors bound at the active site of a blood group A/B synthesizing glycosyltransferase were analysed. The structures and inhibitory patterns of the analogues demonstrate the flexibility of the enzymes which complicates the rational design of glycosyltransferase inhibitors.</p> </abstract>