文献类型：期刊文献

英文题名：A unique and rapid approach toward the efficient development of novel protein tyrosine phosphatase (PTP) inhibitors based on 'clicked' pseudo-glycopeptides

作者：Yang, Jin-Wei[1,2];He, Xiao-Peng[1,2,4,5];Li, Cui[4];Gao, Li-Xin[3];Sheng, Li[3];Xie, Juan[5];Shi, Xiao-Xin[4];Tang, Yun[4];Li, Jia[3];Chen, Guo-Rong[1,2]

机构：[1]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med,Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China;[4]E China Univ Sci & Technol, Dept Pharmaceut Engn, Sch Pharm, Shanghai 200237, Peoples R China;[5]CNRS, ENS Cachan, PPSM, F-94230 Cachan, France

年份：2011

卷号：21

期号：4

起止页码：1092

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000286972400003)】；

基金：Project supported by National Natural Science Foundation of China (Grant Nos. 20876045, 30801405), National Basic Research Program of China (No. 2007CB914201), National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program' (No. 2009ZX09302-001), Shanghai Science and Technology Community (Nos. 10410702700, 09DZ2291200), Chinese Academy of Sciences (No. KSCX2-YW-R-168) and the Fundamental Research Funds for the Central Universities (No. WK1013002). X.-P. H. also gratefully acknowledges the French Embassy in Beijing, PR China for a co-tutored doctoral fellowship.

语种：英文

外文关键词：Glycopeptides; Click reaction; Protein tyrosine phosphatase inhibitor; Microwave irradiation; Docking simulation

摘要：There has been considerable interest in the development of protein tyrosine phosphatase (PTP) inhibitors since many of the PTP members are tightly associated with major human diseases including autoimmune disorders, diabetes and cancer. We report here a unique and rapid approach toward the development of novel PTP inhibitor entities based on triazolyl pseudo-glycopeptides. By employing microwave-accelerated Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC or 'click reaction'), a series of triazole-linked serinyl, threoninyl, phenylalaninyl and tyrosinyl 1-O-gluco- or galactosides have been efficiently synthesized in high yields within only similar to 30 min. Successive biological assay identified these glycopeptidotriazoles as favorable PTP1B and CDC25B inhibitors with selectivity over TCPTP, LAR, SHP-1 and SHP-2. Both the structural diversity of the amino acid (Ser, Thr, Phe and Tyr) introduced and the epimeric identity (Glc or Gal) on monosaccharide scaffold were determined to impact the corresponding inhibitory activity and selectivity. In addition, the benzylated sugar scaffold was demonstrated to act as a crucial role for enhancing the binding affinity of the inhibitors with the targeted PTP. Docking simulation was eventually conducted to propose plausible binding modes of this compound series with PTP1B and CDC25B. Our approach readily realized from naturally abundant raw materials (sugar and amino acid) and via facile, regioselective and expeditious synthetic method (microwave-assisted click reaction) might provide new insights toward the 'click' fabrication of structurally diverse PTP inhibitors. (c) 2010 Elsevier Ltd. All rights reserved.