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Preparation of triazole-linked glycosylated alpha-ketocarboxylic acid derivatives as new PTP1B inhibitors

Song, Z. ; He, X. P. ; Li, C. ; Gao, L. X. ; Wang, Z. X. ; Tang, Y. ; Xie, J. ; Li, J. ; Chen, G. R. ; Carbohydrate Research, 2011, 346(1), 140-145

The synthesis of triazole-linked glycosyl acetophenone, benzoic acid, and alpha-ketocarboxylic acid derivatives was readily achieved via Cu(I)-catalyzed azide-alkyne cycloaddition ('click' reaction) in excellent yields of 93-97%. Among the synthesized glycoconjugates, the triazolyl alpha-ketocarboxylic acids were identified as the most potent protein tyrosine phosphatase 1B (FTP1B) inhibitors with micromole-ranged IC50 values and moderate-to-good selectivity over a panel of homologous PTPs including TCPTP (4.6-fold), LAR (>30-fold), SHP-1 (>30-fold) and SHP-2 (>30-fold). Moreover, a docking simulation was conducted to propose a plausible binding mode of the glucosyl alpha-ketocarboxylic acid triazole with the enzymatic target. (C) 2010 Elsevier Ltd. All rights reserved.

Type :

Publication

Dates :

Paru le 1 janvier 2011

Informations complémentaires :

10.1016/j.carres.2010.10.023