Synthesis and activity on human neutrophil functions of fMLF-OMe analogs containing alkyl spacers at the central position.
We report here the synthesis and activity of new analogs of the N-formyl and N-tert-butyloxycarbonyl (Boc) derivatives of the tripeptide Met-Leu-Phe-OMe containing an achiral omega-amino acid residue replacing the hydrophobic central leucine. The tripeptides HCO-Met-NH-(CH2)n-CO-Phe-OMe and Boc-Met-NH-(CH2)n-CO-Phe-OMe (n = 3-5) containing the central homomorphic residue of 5-aminopentanoic acid (delta-aminovaleric acid; delta-Ava; n = 4) and the two non-homomorphic residues of 4-aminobutanoic acid (gamma-aminobutyric acid; gamma-Abu; n = 3) and 6-aminohexanoic acid (epsilon-aminocaproic acid; epsilon-Aca; n = 5) have been examined. The activity as agonists and antagonists in chemotaxis, lysozyme release, and superoxide anion production of the new analogs has been determined. The N-Boc derivatives 2a and 2b, incorporating the gamma-Abu and the delta-Ava residues, show good and selective antagonist activity on superoxide anion production.
Pagani Zecchini
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G
Dipartimento di Studi Farmaceutici e Centro di Studio per la Chimica del Farmaco del CNR, Università degli Studi di Roma La Sapienza, Italy.
Morera
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E
Nalli
M
M
Paglialunga Paradisi
M
M
Lucente
G
G
Spisani
S
S
D000595:Amino Acid Sequence; D002630:Chemotactic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D002630:Chemotactic Factors; D009240:N-Formylmethionine Leucyl-Phenylalanine