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

页码：3958 / 3966

页数：9

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