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A high potency nonformylated peptide agonist for the phagocyte N-formylpeptide chemotactic receptor.
Gao JL
,
Becker EL
,
Freer RJ
,
Muthukumaraswamy N
,
Murphy PM
.
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Analysis of synthetic tri- and tetrapeptides has previously indicated that N-formylation is required for high biological activity when they react with the phagocyte N-formylpeptide receptor, suggesting that the natural ligand for the receptor is from bacterial and/or mitochondrial sources. To explore this requirement further, we synthesized the pentapeptide methionyl-norleucyl-leucyl-phenylalanyl-phenylalanine (MNleLFF) and studied the effects of different NH2-terminal modifications on its activity. N-formyl-MNleLFF induced transient alterations of [Ca2+]i and superoxide production in human neutrophils with 10- and 100-fold greater potency, respectively, than the proto-type N-formylpeptide, N-formylmethionyl-leucyl-phenylalanine (fMLF). Surprisingly, N-acetyl-MNleLFF was a potent as N-formyl-MNleLFF. Moreover, the unacylated counterpart H-MNleLFF was also highly active, having an EC50 for calcium mobilization of 10 nM, and for respiratory burst activation of 100 nM. All three pentapeptides could completely desensitize calcium transients elicited by stimulation of neutrophils with fMLF, whereas the neutrophil chemoattractants C5a and interleukin 8 only weakly affected fMLF-induced transients, suggesting that they activate neutrophils via the same receptor as fMLF. Finally, all three pentapeptides activated the recombinant human N-formylpeptide receptor expressed in frog oocytes, but did not effectively activate related phagocyte receptors. These data broaden the potential sources of natural ligands for the N-formyl-peptide receptor from N-formylated bacterial and mitochondrial products to other nonformylated endogenous peptides.
Ali,
Differences in phosphorylation of formylpeptide and C5a chemoattractant receptors correlate with differences in desensitization.
1993, Pubmed
Ali,
Differences in phosphorylation of formylpeptide and C5a chemoattractant receptors correlate with differences in desensitization.
1993,
Pubmed
Bao,
Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19.
1992,
Pubmed
Boulay,
Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA.
1990,
Pubmed
Carp,
Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils.
1982,
Pubmed
Didsbury,
Receptor class desensitization of leukocyte chemoattractant receptors.
1991,
Pubmed
Didsbury,
Functional high efficiency expression of cloned leukocyte chemoattractant receptor cDNAs.
1992,
Pubmed
Durstin,
Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes.
1994,
Pubmed
,
Xenbase
Fay,
Evidence for protonation in the human neutrophil formyl peptide receptor binding pocket.
1993,
Pubmed
Freer,
Further studies on the structural requirements for synthetic peptide chemoattractants.
1980,
Pubmed
Gao,
Species and subtype variants of the N-formyl peptide chemotactic receptor reveal multiple important functional domains.
1993,
Pubmed
,
Xenbase
Marasco,
Purification and identification of formyl-methionyl-leucyl-phenylalanine as the major peptide neutrophil chemotactic factor produced by Escherichia coli.
1984,
Pubmed
Murphy,
A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family.
1992,
Pubmed
,
Xenbase
Murphy,
Functional expression of the human formyl peptide receptor in Xenopus oocytes requires a complementary human factor.
1991,
Pubmed
,
Xenbase
Quehenberger,
Multiple domains of the N-formyl peptide receptor are required for high-affinity ligand binding. Construction and analysis of chimeric N-formyl peptide receptors.
1993,
Pubmed
Schiffmann,
N-formylmethionyl peptides as chemoattractants for leucocytes.
1975,
Pubmed
Williams,
Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.
1977,
Pubmed
Ye,
Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor.
1992,
Pubmed