title: C- and N-terminal residue effect on peptide derivatives' antagonism toward the formyl-peptide receptor.
abstract: The biological action of several X-Phe-D-Leu-Phe-D-Leu-Z (X=3',5'-dimethylphenyl-ureido; Z=Phe, Lys, Glu, Tyr) analogues was analysed on human neutrophils to evaluate their ability to antagonize formyl-peptide receptors. X-Phe-D-Leu-Phe-D-Leu-Phe analogues obtained as C-terminal olo or amido derivatives and T-Phe-D-Leu-Phe-D-Leu-Phe analogues (T=thiazolyl-ureido) were also analysed. The activities of pentapeptide derivatives were compared with those of X-Phe-D-Leu-Phe-D-Leu-Phe chosen as reference antagonist. Our results demonstrate that X-Phe-D-Leu-Phe-D-Leu-Phe-olo, X-Phe-D-Leu-Phe-D-Leu-Glu and X-Phe-D-Leu-Phe-D-Leu-Tyr are more active antagonists than X-Phe-D-Leu-Phe-D-Leu-Phe. The presence of Lys (X-Phe-D-Leu-Phe-D-Leu-Lys) seems, instead, to inhibit the formyl-peptide receptor antagonist properties. The presence of the N-terminal thiazolyl-ureido group seems to considerably contribute to the receptor antagonist properties of T-Phe-D-Leu-Phe-D-Leu-Phe-OH. The introduction of the C-terminal methyl ester (T-Phe-D-Leu-Phe-D-Leu-Phe-OMe) or amido group (X-Phe-D-Leu-Phe-D-Leu-Phe-NH2) appears detrimental for the affinity and formyl-peptide receptor antagonist properties of the Phe-D-Leu-Phe-D-Leu-Phe derivatives. The examined peptides inhibit superoxide anion production and lysozyme release more efficaciously than neutrophil chemotaxis.
authors.affiliation: Department of Pharmaceutical Sciences, Ferrara University, via Fossato di Mortara 19, 44100 Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dalpiaz
authors.forename: Maria E
authors.initials: ME
authors.lastname: Ferretti
authors.forename: Gianni
authors.initials: G
authors.lastname: Vertuani
authors.forename: Serena
authors.initials: S
authors.lastname: Traniello
authors.forename: Angelo
authors.initials: A
authors.lastname: Scatturin
authors.forename: Susanna
authors.initials: S
authors.lastname: Spisani
mesh_terms: D000595:Amino Acid Sequence; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009113:Muramidase