文献类型：期刊文献

英文题名：Facile fabrication of promising protein tyrosine phosphatase (PTP) inhibitor entities based on 'clicked' serine/threonine-monosaccharide hybrids

作者：He, Xiao-Peng[1,2,3,4];Deng, Qiong[2,3,4];Gao, Li-Xin[5];Li, Cui[2,3,4];Zhang, Wei[5];Zhou, Yu-Bo[5];Tang, Yun[2,3,4];Shi, Xiao-Xin[2,3,4];Xie, Juan[1];Li, Jia[5];Chen, Guo-Rong[2,3,4];Chen, Kaixian[2,3,4,5]

机构：[1]CNRS, ENS Cachan, PPSM, Inst Alembert,UMR 8531, F-94235 Cachan, France;[2]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[5]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Natl Ctr Drug Screening, Shanghai 201203, Peoples R China

年份：2011

卷号：19

期号：13

起止页码：3892

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000291934700002)】；

基金：Project supported by National Natural Science Foundation of China (Grant Nos. 20876045 and 30801405), National Basic Research Program of China (No. 2007CB914201), Shanghai Science and Technology Community (No. 10410702700), Chinese Academy of Sciences (No. KSCX2-EW-R-15) and the Fundamental Research Funds for the Central Universities (No. WK1013002). X.-P. also gratefully acknowledges the French Embassy in PR China for a co-tutored doctoral fellowship.

语种：英文

外文关键词：Sugar template; Click chemistry; Amino acid; PTP inhibitor; MTT assay

摘要：Protein tyrosine phosphatases (PTPs) are well-validated therapeutic targets for many human major diseases. The development of their potent inhibitors has therefore become a main focus of both academia and the pharmaceutical industry. We report herein a facile strategy toward the fabrication of new and competent PTP inhibitor entities by simply 'clicking' alkynyl amino acids onto diverse azido sugar templates. Triazolyl glucosyl, galactosyl, and mannosyl serine and threonine derivatives were efficiently synthesized via click reaction, which were then identified as potent CDC25B and PTP1B inhibitors selective over a panel of homologous PTPs tested. Their inhibitory activity and selectivity were found to largely lie on the structurally and configurationally diversified monosaccharide moieties whereon serinyl and threoninyl residues were introduced. In addition, MTT assay revealed the triazole-connected sugar-amino acid hybrids may also inhibit the growth of several human cancer cell lines including A549, Hela, and especially HCT-116. On the basis of such compelling evidence, we consider that this compound series could furnish promising chemical entities serving as new CDC25B and PTP1B inhibitors with potential cellular activity. Furthermore, the 'click' strategy starting from easily accessible and biocompatible amino acids and sugar templates would allow the modular fabrication of a rich library of new PTP inhibitors efficaciously and productively. (C) 2011 Elsevier Ltd. All rights reserved.