Chemotactic peptides: fMLF-OMe analogues incorporating proline–methionine chimeras as N-terminal residue

The new fMLF analogues 1–4, incorporating chimeric S-proline–methionine residues (namely the homochiral cis-4(S)-methylthio-(S)-proline (10) and the heterochiral trans-4(R)-methylthio-(S)-proline) (17) in place of the native S-methionine, have been prepared; their solution conformation and activity as agonists or antagonists of formylpeptide receptors have been studied. In addition to peptides 1–4, which maintain the Met γ-thiomethyl-ether function, the analogues Boc-PLF-OMe (18) and For-PLF-OMe (19) devoid, as compared with 1–4, of position 1 side chain, have been synthesized and their activity examined.

Novel analogues of the potent chemotactic tripeptide fMLF were designed and synthesized. The representative compound (1) containing the cis-4(S)-methylthio-(S)-proline residue at position 1 and the N-Boc-protecting group resulted to be a pure chemoattractant with the highest activity.Figure optionsDownload as PowerPoint slide