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

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. 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.