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 journalArticlepeer-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 languageAmerican English
Pages (from-to)3958-3966
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number13
DOIs
StatePublished - 1 Jul 2013

Keywords

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

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