title: Synthesis and biological evaluation of new active For-Met-Leu-Phe-OMe analogues containing para-substituted Phe residues.
abstract: In the present study, we report synthesis and biological evaluation of the N-Boc-protected tripeptides 4a-l and N-For protected tripeptides 5a-l as new For-Met-Leu-Phe-OMe (fMLF-OMe) analogues. All the new ligands are characterized by the C-terminal Phe residue variously substituted at position 4 of the aromatic ring. The agonism of 5a-l and the antagonism of 4a-l (chemotaxis, superoxide anion production, lysozyme release as well as receptor binding affinity) have been examined on human neutrophils. No synthesized compounds has higher activity than the standard fMLF-OMe tripeptide to stimulate chemotaxis, although compounds 5a and 5c with -CH(3) and -C(CH(3))(3), respectively, in position 4 on the aromatic ring, are better than the standard tripeptide to stimulate the production of superoxide anion, in higher concentration. Compounds 4f and 4i, containing -F and -I in position 4, respectively, on the aromatic ring of phenylalanine, exhibit significant chemotactic antagonism. The influence of the different substitution at the position 4 on the aromatic ring of phenylalanine is discussed.
authors.affiliation: Dipartimento di Scienze del Farmaco, Università di Chieti-Pescara G. d'Annunzio, Via dei Vestini 31, 66100 Chieti, Italy. a.mollica@unich.it
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Federica
authors.initials: F
authors.lastname: Feliciani
authors.forename: Azzurra
authors.initials: A
authors.lastname: Stefanucci
authors.forename: Roberto
authors.initials: R
authors.lastname: Costante
authors.forename: Gino
authors.initials: G
authors.lastname: Lucente
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Daniela
authors.initials: D
authors.lastname: Notaristefano
authors.forename: Susanna
authors.initials: S
authors.lastname: Spisani
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000037:antagonists & inhibitors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D008968:Molecular Conformation; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010649:Phenylalanine / Q000737:chemistry*; D012016:Reference Values; D013237:Stereoisomerism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000838:Anions; D009842:Oligopeptides; D013481:Superoxides; D010649:Phenylalanine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D009113:Muramidase