Trp-Arg-Xaa tripeptides act as uncompetitive-type inhibitors of human dipeptidyl peptidase IV
Trp-Arg-Xaa tripeptides act as uncompetitive-type inhibitors of human dipeptidyl peptidase IV
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DOI：
10.1016/j.peptides.2014.01.027
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发表时间：
2014-04-01
期刊：
影响因子：
3
通讯作者：
Kawarasaki, Yasuaki
中科院分区：
文献类型：
--
作者：
Vu Thi Tuyet Lan;Ito, Keisuke;Kawarasaki, Yasuaki
人二肽基肽酶 IV（hDPPIV，别名：CD26）抑制剂为治疗 2 型糖尿病提供了有效的策略。最近，我们课题组通过对二肽库的系统分析，发现了一种非模拟底物抑制性二肽Trp-Arg。在本研究中，分析了三肽文库 Trp-Arg-Xaa（其中 Xaa 代表任何氨基酸），以研究肽能抑制剂与 hDPPIV 的相互作用。 Trp-Arg-Glu 对 hDPPIV 显示出最高的抑制效果 (Ki= 130 p,M)。所有测试的 19 种 Trp-Arg-Xaa 三肽均表现出独特的非竞争性抑制作用。基于hDPPIV的晶体结构讨论了Trp-Arg-Xaa的抑制机制。本研究获得的信息提出了开发 hDPPIV 抑制肽和药物的新概念。 (c) 2014 Elsevier Inc. 保留所有权利。
Human dipeptidyl peptidase IV (hDPPIV, alternative name: CD26) inhibitors provide an effective strategy for the treatment of type 2 diabetes. Recently, our research group discovered a non substrate-mimic inhibitory dipeptide, Trp-Arg, by the systematic analysis of a dipeptide library. In the present study, a tripeptide library Trp-Arg-Xaa (where Xaa represents any amino acid) was analyzed to investigate the interactions of peptidergic inhibitors with hDPPIV. Trp-Arg-Glu showed the highest inhibitory effect toward hDPPIV (Ki= 130 p,M). All of the tested 19 Trp-Arg-Xaa tripeptides showed unique uncompetitivetype inhibition. The inhibition mechanism of Trp-Arg-Xaa is discussed based on the crystal structure of hDPPIV. The information obtained by this study suggests a novel concept for developing hDPPIV inhibitory peptides and drugs. (c) 2014 Elsevier Inc. All rights reserved.