Stabilized β‑Hairpin
Peptide Inhibits
Insulin Degrading Enzyme
Dan Yang
Weirong Qin
Xiaodong Shi
Bili Zhu
Mingsheng Xie
Hui Zhao
Bin Teng
Yujie Wu
Rongtong Zhao
Feng Yin
Peigen Ren
Lizhong Liu
Zigang Li
10.1021/acs.jmedchem.8b00418.s001
https://acs.figshare.com/articles/journal_contribution/Stabilized_Hairpin_Peptide_Inhibits_Insulin_Degrading_Enzyme/7056524
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 β-hairpin
peptide that can efficiently inhibit the enzymatic activity of IDE.
The resulting stabilized peptide <b>B35</b> is demonstrated
to activate the AKT phosphorylation pathway in skeletal muscle cells
and is shown to slow insulin degradation. An 80 mg kg<sup>–1</sup> intraperitoneal (i.p.) injection of the stabilized β-hairpin
peptide <b>B35</b> 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 <i>in vitro</i> and <i>in vivo</i> assays,
even at high concentrations (300 μM). This study suggests that
IDE peptide inhibitors could function as potentially meaningful candidates
for the development of type-2 diabetes therapeutics.
2018-08-27 00:00:00
type -2 diabetes therapeutics
insulin degradation
IDE peptide inhibitors
β- hairpin peptide
type -2 diabetes
β- hairpin peptide B 35
novel IDE inhibitors
vivo assays
muscle cells
peptide B 35
glucose tolerance test
AKT phosphorylation pathway
glucose tolerance
novel therapeutics
mouse model