Download MendeleyDesign of glycosyltransferase inhibitors: pyridine as a pyrophosphate surrogate.
Wang, S., Cuesta-Seijo, J.A., Lafont, D., Palcic, M.M., Vidal, S.(2013) Chemistry 19: 15346-15357
- PubMed: 24108680
- DOI: https://doi.org/10.1002/chem.201301871
- Primary Citation of Related Structures:
4KC1, 4KC2, 4KC4 - PubMed Abstract:
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 Mn(2+) ion causing a slight displacement (2 ?) 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.
Organizational Affiliation:
Institut de Chimie et Biochimie Mol¨¦culaires et Supramol¨¦culaires, Laboratoire de Chimie Organique 2, Glycochimie, UMR 5246, CNRS and Universit¨¦ Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 6922 Villeurbanne (France), Fax: (+33)?472-448-109.
