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

Mattan Hurevich; Maya Ratner-Hurevich; Yftah Tal-Gan; Deborah E. Shalev; Shlomo Z. Ben-Sasson; Chaim Gilon

doi:10.1016/j.bmc.2013.03.019

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

Mattan Hurevich, Maya Ratner-Hurevich, Yftah Tal-Gan, Deborah E. Shalev, Shlomo Z. Ben-Sasson, Chaim Gilon

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	English
Pages (from-to)	3958-3966
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2013.03.019
State	Published - 1 Jul 2013

Keywords

Backbone cyclization
G protein-coupled receptors
GPCR dimerization
Helix mimetics
Multiple Sclerosis
Urea cyclization

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2013.03.019

Cite this

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

abstract = "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",

keywords = "Backbone cyclization, G protein-coupled receptors, GPCR dimerization, Helix mimetics, Multiple Sclerosis, Urea cyclization",

author = "Mattan Hurevich and Maya Ratner-Hurevich and Yftah Tal-Gan and Shalev, {Deborah E.} and Ben-Sasson, {Shlomo Z.} and Chaim Gilon",

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doi = "10.1016/j.bmc.2013.03.019",

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T2 - A rational approach for inhibiting dimerization of G protein-coupled receptors

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AU - Ratner-Hurevich, Maya

AU - Tal-Gan, Yftah

AU - Shalev, Deborah E.

AU - Ben-Sasson, Shlomo Z.

AU - Gilon, Chaim

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AB - 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

KW - Backbone cyclization

KW - G protein-coupled receptors

KW - GPCR dimerization

KW - Helix mimetics

KW - Multiple Sclerosis

KW - Urea cyclization

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DO - 10.1016/j.bmc.2013.03.019

M3 - مقالة

C2 - 23706536

SN - 0968-0896

VL - 21

SP - 3958

EP - 3966

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 13

ER -

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

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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