Exploration of biguanido-oxovanadium complexes as potent and selective inhibitors of protein tyrosine phosphatases

被引：23
作者：
Lu, Liping [1 ]
Gao, Xiaoli [1 ,2 ]
Zhu, Miaoli [1 ]
Wang, Sulian [1 ]
Wu, Qiong [3 ]
Xing, Shu [3 ]
Fu, Xueqi [3 ]
Liu, Zhiwei [4 ]
Guo, Maolin [4 ]
机构：
[1] Shanxi Univ, Educ Minist, Inst Mol Sci, Key Lab Chem Biol & Mol Engn, Taiyuan 030006, Shanxi, Peoples R China
[2] Taiyuan Normal Univ, Dept Chem, Taiyuan 030001, Peoples R China
[3] Jilin Univ, Coll Life Sci, Edmond H Fischer Signal Transduct Lab, Changchun 130023, Peoples R China
[4] Univ Massachusetts, Dept Chem & Biochem, UMass Cranberry Hlth Res Ctr, Dartmouth, MA 02747 USA
来源：
BIOMETALS | 2012年 / 25卷 / 03期
基金：
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词：
Biguanido-oxovanadium complexes; Protein tyrosine phosphatases; Competitive inhibition; Selective inhibition; STRUCTURE-BASED DESIGN; INSULIN SENSITIVITY; NEGATIVE REGULATOR; CATALYTIC DOMAIN; COPPER-COMPLEXES; SCHIFF-BASE; VANADIUM; GLUCOSE; DERIVATIVES; MECHANISM;
D O I：
10.1007/s10534-012-9548-4
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The inhibitory effects of three biguanido-oxovanadium complexes ([VO(L1-3)(2)]center dot nH(2)O: HL1 = metformin, HL2 = phenformin, HL3 = moroxydine) against four protein tyrosine phosphatases (PTPs) and an alkaline phosphatase (ALP) were investigated. The complexes display strong inhibition against PTP1B and TCPTP (IC50, 80-160 nM), a bit weaker inhibition against HePTP (IC50, 190-410 nM) and SHP-1(IC50, 0.8-3.3 mu M) and much weaker inhibition against ALP (IC50, 17-35 mu M). Complex is about twofold less potent against PTP1B, TCPTP and HePTP than complexes and , while complex inhibits SHP-1 more strongly (about three to fourfold) than the other two complexes. These results suggest that the structures of the ligands slightly influence the potency and selectivity against PTPs. The complexes inhibit PTP1B and ALP with a typical competitive type.
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收藏
页码：599 / 610
页数：12
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