Synthesis and bioactivity of chemotactic tetrapeptides: fMLF-OMe analogues incorporating spacer aminoacids at the lateral positions.
A small library of N-For and N-Boc tetrapeptidic analogues of the chemotactic tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe), obtained by incorporating three different spacer aminoacids (Gly, betaAla and Pro) between the native residues of Met and Leu (N-For- and N-Boc-Met-Xaa-Leu-Phe-OMe; Xaa2 series) and Leu and Phe (N-For- and N-Boc-Met-Leu-Xaa-Phe-OMe; Xaa3 series), have been synthesized and examined for their biological activity as agonists and antagonists. Chemotaxis, lysozyme release and superoxide anion production have been measured. All the N-For analogues maintain good to moderate chemotactic activity with the betaAla3 15 model reaching the maximum value. All the N-Boc tetrapeptides are efficient chemotactic antagonists. Conversely, with the exception of the moderate antagonistic activity exhibited by the N-Boc Xaa2 models against lysozyme release, all the other N-Boc analogues do not show significant activity against both superoxide anion and lysozyme release.
Lucente
Gino
G
Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Rome, Italy. gino.lucente@uniroma1.it
Giordano
Cesare
C
Sansone
Anna
A
Torino
Domenica
D
Spisani
Susanna
S
D000596:Amino Acids / Q000737:chemistry; D002630:Chemotactic Factors / Q000737:chemistry / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006801:Humans; D015394:Molecular Structure; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism
D000596:Amino Acids; D002630:Chemotactic Factors; D010455:Peptides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester