title: Identification of peptide ligands to the chemokine receptor CCR5 and their maturation by gene shuffling.
abstract: The determination of protein-protein interactions and their role in diverse pathophysiological processes is a promising approach to the identification of molecules of therapeutic potential. This paper describes the identification of peptidic CCR5 receptor ligands as potential drug leads against HIV-1 infection using in vitro evolution based on phage display. A phage-displayed peptide library was used to select for anti-CCR5 peptide. Further in vitro evolution of the peptide by exon shuffling was performed to identify peptides with optimized characteristics for CCR5 receptor. This peptide inhibited HIV coreceptor activity in a cell fusion assay with an IC50 of 5 microM. It did not exhibit either agonistic or antagonistic activity on CCR5 in the concentration range used. To our knowledge, this is a first report that describes the identification of peptide ligands specific to the CCR5 receptor from a phage-displayed library and the maturation of the selected peptide sequence by gene shuffling.
authors.affiliation: Institute of Biotechnology, University of Lausanne, 1005 Lausanne, Switzerland.
authors.forename: Eva Cachin
authors.initials: EC
authors.lastname: Vyroubalova
authors.forename: Oliver
authors.initials: O
authors.lastname: Hartley
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mermod
authors.forename: Igor
authors.initials: I
authors.lastname: Fisch
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D032621:DNA Shuffling; D019020:Directed Molecular Evolution; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008561:Membrane Fusion / Q000187:drug effects; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D019713:Receptors, CCR5 / Q000819:agonists / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D019713:Receptors, CCR5