title: A formyl peptide substituted with a conformationally constrained phenylalanine residue evokes a selective immune response in human neutrophils.
abstract: Formyl-Met-Leu-Phe-OH (fMLP) binds to formyl peptide receptors, FPR1 and FPR2, and evokes migration and superoxide anion production in human neutrophils. To obtain a more effective and selective ligand, fMLP analogs in which the Phe residue was substituted with four isomers of cyclopropanephenylalanine were synthesized. While Z-isomer peptides induced both migration and superoxide anion production, E-isomer peptides elicited only chemotaxis. Homologous receptor desensitization experiments revealed that E-isomer peptides bound to FPR2. Although a selective agonist of chemotaxis also binds to FPR2 without increasing intracellular calcium concentration, E-isomer peptide elevated the concentration to the same level as fMLP. Understanding of mechanisms responsible for the selectivity of the reported selective agonists and ∇Phe-substituted analogs should prove useful for revealing the relationship between receptor-ligand interactions and biological responses of human neutrophils.
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Saga University, 1 Honjo-machi, Saga 840-8502, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayashi
authors.forename: Masaya
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Osada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fujita
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kodama
mesh_terms: D006801:Humans; D008968:Molecular Conformation; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010649:Phenylalanine / Q000737:chemistry*; D012016:Reference Values
chemical_list: D010455:Peptides; D010649:Phenylalanine