Met-Ile-Phe-Leu derivatives: full and partial agonists of human neutrophil formylpeptide receptors.
The biological action of a series of Met-Ile-Phe-Leu analogues was analyzed on human neutrophils, to evaluate their ability to interact with formylpeptide receptors and to induce the related neutrophil responses. Three in vitro assays were carried out: receptor binding, chemotaxis and superoxide anion release. Our results demonstrate that formyl-Met-Ile-Phe-Leu derivatives act as more potent full agonists than formyl-Met-Leu-Phe, the tripeptide normally used as a model chemoattractant for the study of cell functions. On the other hand, the presence of N-ureidoisopropyl substituent in tetrapeptides imparts weak partial agonist properties. It has furthermore been demonstrated that the C-terminal methyl esterification or amination weakly influences the properties of tetrapeptide homologues. Finally, t-Boc-Met-Ile-Phe-Leu derivatives do not appear able to interact with formylpeptide receptors.
Dalpiaz
A
A
Department of Pharmaceutical Science, Ferrara University, via Fossato di Mortara 19, 44100 Ferrara, Italy.
Scatturin
A
A
Vertuani
G
G
Pecoraro
R
R
Borea
P A
PA
Varani
K
K
Traniello
S
S
Spisani
S
S
D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000819:agonists*; D018000:Receptors, Peptide / Q000819:agonists*; D013481:Superoxides / Q000378:metabolism
D009842:Oligopeptides; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D013481:Superoxides