Synthesis and bioactivity of chemotactic tetrapeptides: fMLF-OMe analogues incorporating spacer aminoacids at the lateral positions

Amino Acids. 2009 Jul;37(2):285-95. doi: 10.1007/s00726-008-0145-3. Epub 2008 Jul 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Chemotactic Factors* / chemistry
  • Chemotactic Factors* / metabolism
  • Chemotaxis, Leukocyte / physiology*
  • Humans
  • Molecular Structure
  • N-Formylmethionine Leucyl-Phenylalanine / analogs & derivatives*
  • N-Formylmethionine Leucyl-Phenylalanine / chemistry
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Neutrophils / cytology
  • Neutrophils / metabolism
  • Peptides* / genetics
  • Peptides* / metabolism

Substances

  • Amino Acids
  • Chemotactic Factors
  • Peptides
  • N-Formylmethionine Leucyl-Phenylalanine
  • formylmethionyl-leucyl-phenylalanine methyl ester