Novel DOCK2-selective inhibitory peptide that suppresses B-cell line migration

被引：21

作者：

Sakamoto, Kotaro ^{[1
]}

Adachi, Yusuke ^{[1
]}

Komoike, Yusaku ^{[1
]}

Kamada, Yusuke ^{[1
]}

Koyama, Ryokichi ^{[1
]}

Fukuda, Yasunori ^{[1
]}

Kadotani, Akito ^{[1
]}

Asami, Taiji ^{[1
]}

Sakamoto, Jun-ichi ^{[1
]}

机构：

[1] Takeda Pharmaceut Co Ltd, Div Pharmaceut Res, 26-1,Muraoka Higashi 2 Chome, Fujisawa, Kanagawa 2518555, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 483卷 / 01期

关键词：

Peptide; DOCK2; PPI; CPP; Cell migration; Phage display; T7 PHAGE DISPLAY; PENETRATING PEPTIDES; NATURAL-PRODUCTS; PROTEIN; DISCOVERY; DOCK2; IDENTIFICATION; LYMPHOCYTE; MOTIF;

D O I：

10.1016/j.bbrc.2016.12.170

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：

Dedicator of cytokinesis 2 (DOCK2) is a key molecule for lymphocyte activation and migration. DOCK2 interacts with Ras-related C3 botulinus toxin substrate 1 (Rac1, GTPase) and mediates the GDP-GTP exchange reaction, indicating that inhibitors against protein-protein interaction (PPI) between DOCK2 and Rac1 would be good drug candidates for treating immune-related disorders. Here, we report DOCK2selective PPI inhibitory peptides discovered using random peptide T7 phage display technology. These peptides inhibited DOCK2 activity at nanomolar concentrations and were delivered to intracellular compartments by combination with cell-penetrating peptide (CPP). Consequently, one peptide, R4-DCpep-2(V2W/ K4R/ ox)-NH2 (Ac-RRRRCWARYHGYPWCRRRR-NH2), inhibited migration in human B lymphocyte MINO cell line at IC50 = 120 nM. To our knowledge, this is the first report of a DOCK2-selective peptide inhibitor; this study will contribute to the development of novel DOCK2-targeting immunosuppressive drugs. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：183 / 190

页数：8

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