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^*

^*Corresponding author for this work

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

13 Scopus citations

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

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10.1016/j.bmc.2013.03.019

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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",

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AU - Tal-Gan, Yftah

AU - Shalev, Deborah E.

AU - Ben-Sasson, Shlomo Z.

AU - Gilon, Chaim

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

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Keywords

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