Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors

被引：21

作者：

Tanegashima, Kosuke ^{[1
]}

Tsuji, Kohei ^{[2
,3
]}

Suzuki, Kenji ^{[1
,4
]}

Shigenaga, Akira ^{[2
,3
]}

Otaka, Akira ^{[2
,3
]}

Hara, Takahiko ^{[1
]}

机构：

[1] Tokyo Metropolitan Inst Med Sci, Stem Cell Project, Setagaya Ku, Tokyo 1568506, Japan

[2] Univ Tokushima, Inst Hlth Biosci, Tokushima 7708505, Japan

[3] Univ Tokushima, Grad Sch Pharmaceut Sci, Tokushima 7708505, Japan

[4] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Cell Biol, Bunkyo Ku, Tokyo 1138549, Japan

来源：

FEBS LETTERS | 2013年 / 587卷 / 23期

关键词：

CXCL14; CXCL12; CXCR4; alpha-Helix; CHEMOKINE RECEPTOR; FACTOR-I; INTERLEUKIN-8; METASTASIS; BINDING; ANALOGS;

D O I：

10.1016/j.febslet.2013.10.017

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：

We recently reported that CXCL14 binds to CXCR4 with high affinity and inhibits CXCL12-mediated chemotaxis. Here we found that the C-terminal 51-77 amino acid residues of CXCL14 are responsible for CXCR4 binding. A disulfide dimer peptide of CXCL14(51-77) bound to CXCR4 with comparable affinity to full length CXCL14, and exhibited CXCL12 inhibitor activity. CXCR4 was efficiently internalized upon binding of dimeric CXCL14(51-77), thereby being reduced on the cell surface. Substitution of 5 amino acid residues in combination with the use of an oxime linker for dimerization increased the solubility and chemical stability of the dimeric CXCL14(51-77). Structured summary of protein interactions: CXCL14 physically interacts with CXCL14 by anti tag coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：3770 / 3775

页数：6

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