Backbone cyclic helix mimetic of chemokine (C-C motif) receptor 2: A rational approach for inhibiting dimerization of G protein-coupled receptors

被引：10
作者：
Hurevich, Mattan [1 ]
Ratner-Hurevich, Maya [2 ]
Tal-Gan, Yftah [1 ]
Shalev, Deborah E. [3 ]
Ben-Sasson, Shlomo Z. [2 ]
Gilon, Chaim [1 ]
机构：
[1] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel
[2] Hadassah Hebrew Univ Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel
[3] Hebrew Univ Jerusalem, Wolfson Ctr Appl Struct Biol, IL-91904 Jerusalem, Israel
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 13期
关键词：
G protein-coupled receptors; Backbone cyclization; Helix mimetics; Urea cyclization; GPCR dimerization; Multiple Sclerosis; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; RING-CLOSING METATHESIS; SOLID-PHASE SYNTHESIS; MACROPHAGE RECRUITMENT; MULTIPLE-SCLEROSIS; BUILDING UNITS; ALPHA-HELICES; PEPTIDES; CCR2;
D O I：
10.1016/j.bmc.2013.03.019
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：
The transmembrane helical bundle of G protein-coupled receptors (GPCRs) dimerize through helix-helix interactions in response to inflammatory stimulation. A strategy was developed to target the helical dimerization site of GPCRs by peptidomimetics with drug like properties. The concept was demonstrated by selecting a potent backbone cyclic helix mimetic from a library that derived from the dimerization region of chemokine (C-C motif) receptor 2 (CCR2) that is a key player in Multiple Sclerosis. We showed that CCR2 based backbone cyclic peptide having a stable helix structure inhibits specific CCR2-mediated chemotactic migration (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3958 / 3966
页数：9
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