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.
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Mattan
authors.initials: M
authors.lastname: Hurevich
authors.forename: Maya
authors.initials: M
authors.lastname: Ratner-Hurevich
authors.forename: Yftah
authors.initials: Y
authors.lastname: Tal-Gan
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Shalev
authors.forename: Shlomo Z
authors.initials: SZ
authors.lastname: Ben-Sasson
authors.forename: Chaim
authors.initials: C
authors.lastname: Gilon
mesh_terms: D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology*; D055503:Protein Multimerization / Q000187:drug effects*; D017433:Protein Structure, Secondary; D054390:Receptors, CCR2 / Q000737:chemistry* / Q000378:metabolism*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology
chemical_list: D010456:Peptides, Cyclic; D057786:Peptidomimetics; D054390:Receptors, CCR2; D014508:Urea