Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors

doi:10.1039/c0nj00835d

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	Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors
	He, Xiao-Peng 2,3,4,5; Li, Cui 5; Jin, Xiao-Ping 3,4; Song, Zhuo 3,4; Zhang, Hai-Lin 3,4; Zhu, Cheng-Jiang 2,3,4; Shen, Qiang 1; Zhang, Wei 1; Sheng, Li 1; Shi, Xiao-Xin 5
刊名	NEW JOURNAL OF CHEMISTRY
	2011
卷号	35 期号:3 页码:622-631
ISSN号	1144-0546
DOI	10.1039/c0nj00835d
文献子类	Article
英文摘要	There has been increasing interest in the development of protein tyrosine phosphatase 1B (PTP1B) inhibitors for the treatment of type 2 diabetes, obesity and breast cancer. We report here the identification of a series of mono-and bis-phenylalaninyl and tyrosinyl glucoside derivatives as novel PTP1B inhibitors. The designed compounds bearing one or two phenylalanine or tyrosine derivatives on the 6-, 2,3-, 2,6-, 3,4- and 4,6-positions of the glucosyl scaffolds were efficiently constructed via the microwave-assisted Cu(I)-catalyzed azide-alkyne cycloaddition in moderate-to-excellent yields. Successive biological assays identified these compounds as novel PTP1B inhibitors, with the 4,6-disubstituted tyrosinyl glucoside being the most potent. A kinetic study established that both mono-and bis-triazole-linked glycosyl acids act as typical competitive inhibitors whereas the bis-triazolyl ester that also exhibited inhibitory activity on PTP1B displayed a mixed-type inhibition pattern. Furthermore, docking simulation plausibly proposed the diverse binding modes of these compounds with the enzymatic target.
资助项目	French Embassy in Beijing, China[00000000] ; French Ministry of Foreign Affairs[00000000] ; CNRS[00000000] ; ENS Cachan[00000000] ; National Natural Science Foundation of China[20876045] ; National Natural Science Foundation of China[30801405] ; National Basic Research Program of China[2007CB914201] ; National Science & Technology Major Project of China "Key New Drug Creation and Manufacturing Program''[2009ZX09302-001] ; Shanghai Science and Technology Community[10410702700] ; Shanghai Science and Technology Community[09DZ2291200] ; Chinese Academy of Sciences[KSCX2-YW-R-168]
WOS关键词	TYROSINE-PHOSPHATASE 1B ; 1,3-DIPOLAR CYCLOADDITION REACTION ; INSULIN SENSITIVITY ; C-GLYCOSYL ; GLYCOGEN-PHOSPHORYLASE ; COMPETITIVE INHIBITOR ; CLICK CHEMISTRY ; BINDING-SITE ; PROTEIN ; DISCOVERY
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000287867300016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278668]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物安全性评价中心
通讯作者	Li, Jia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.CNRS, ENS Cachan, UMR 8531, PPSM,Inst dAlembert, F-94235 Cachan, France; 3.E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China; 4.E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China; 5.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	He, Xiao-Peng,Li, Cui,Jin, Xiao-Ping,et al. Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors[J]. NEW JOURNAL OF CHEMISTRY,2011,35(3):622-631.
APA	He, Xiao-Peng.,Li, Cui.,Jin, Xiao-Ping.,Song, Zhuo.,Zhang, Hai-Lin.,...&Xie, Juan.(2011).Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors.NEW JOURNAL OF CHEMISTRY,35(3),622-631.
MLA	He, Xiao-Peng,et al."Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors".NEW JOURNAL OF CHEMISTRY 35.3(2011):622-631.