Design of Glycosyltransferase Inhibitors: Pyridine as a Pyrophosphate Surrogate. Issue 45 (23rd September 2013)

• Record Type: Journal Article
• Authors: Wang, Shuai; Cuesta‐Seijo, Jose A.; Lafont, Dominique; Palcic, Monica M.; Vidal, Sébastien
• Is Part Of: Chemistry. Volume 19:Issue 45(2013)
• Page Start: 15346
• Page End: 15357
• Publication Date: 2013-09-23
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201301871
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A series of ten glycosyltransferase inhibitors has been designed and synthesized by using pyridine as a pyrophosphate surrogate. The series was prepared by conjugation of carbohydrate, pyridine, and nucleoside building blocks by using a combination of glycosylation, the Staudinger–Vilarrasa amide‐bond formation, and azide–alkyne click chemistry. The compounds were evaluated as inhibitors of five metal‐dependent galactosyltransferases. Crystallographic analyses of three inhibitors complexed in the active site of one of the enzymes confirmed that the pyridine moiety chelates the Mn²⁺ ion causing a slight displacement (2 Å) from its original position. The carbohydrate head group occupies a different position than in the natural uridine diphosphate (UDP)–Gal substrate with little interaction with the enzyme.</p> </abstract>