Stabilized beta-Hairpin Peptide Inhibits Insulin Degrading Enzyme

	Stabilized beta-Hairpin Peptide Inhibits Insulin Degrading Enzyme
	Xie, Mingsheng; Ren, Peigen; Teng, Bin; Yin, Feng; Li, Zigang; Liu, Lizhong; Zhao, Rongtong; Wu, Yujie; Yang, Dan; Qin, Weirong
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2018
文献子类	期刊论文
英文摘要	Insulin-degrading enzyme (IDE) plays a critical role in both the proteolytic degradation and inactivation of insulin. The exploration of novel IDE inhibitors could aid in the study of novel therapeutics for type-2 diabetes. Herein, we report a hypothesized stabilized beta-hairpin peptide that can efficiently inhibit the enzymatic activity of IDE. The resulting stabilized peptide B35 is demonstrated to activate the AKT phosphorylation pathway in skeletal muscle cells and is shown to slow insulin degradation. An 80 mg kg(-1) intraperitoneal (i.p.) injection of the stabilized beta-hairpin peptide B35 is demonstrated to improve glucose tolerance during an oral glucose tolerance test in obese mouse model. We note that this stabilized peptide exhibited negligible cytotoxicity in both in vitro and in vivo assays, even at high concentrations (300 mu M). This study suggests that IDE peptide inhibitors could function as potentially meaningful candidates for the development of type-2 diabetes therapeutics.
URL标识	查看原文
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/14432]
专题	深圳先进技术研究院_医工所
推荐引用方式 GB/T 7714	Xie, Mingsheng,Ren, Peigen,Teng, Bin,et al. Stabilized beta-Hairpin Peptide Inhibits Insulin Degrading Enzyme[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018.
APA	Xie, Mingsheng.,Ren, Peigen.,Teng, Bin.,Yin, Feng.,Li, Zigang.,...&Zhao, Hui.(2018).Stabilized beta-Hairpin Peptide Inhibits Insulin Degrading Enzyme.JOURNAL OF MEDICINAL CHEMISTRY.
MLA	Xie, Mingsheng,et al."Stabilized beta-Hairpin Peptide Inhibits Insulin Degrading Enzyme".JOURNAL OF MEDICINAL CHEMISTRY (2018).