Novel chemotactic For-Met-Leu-Phe-OMe (fMLF-OMe) analogues based on met residue replacement by 4-amino-proline scaffold: synthesis and bioactivity.

Abstract cis -(2 S ,4 S ) 4-Amino-proline (cAmp) and trans -(2 S ,4 R ) 4-amino-proline (tAmp) residues, bearing N -For or N -Boc substituents at the two amino groups, have been incorporated into the potent chemotactic agent fMLF-OMe in place of the N-terminal native ( S )-methionine to give the analogues 17a – 19a and 17b – 19b . The new ligands have been examined for their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils as agonists and antagonists. Compounds 19a and 19b , bearing two N -For groups at the proline scaffold, are active and selective chemoattractants. The ligand 18b , containing N -For at the 4-amino group of the N -Boc-tAmp residue, exhibits significant chemotactic antagonism. The influence of the different substitution at the N-terminal position of the new analogues is discussed.