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

cis-(2S,4S)4-Amino-proline(cAmp)and trans-(2S,4R)4-amino-proline(tAmp)residues,bearing N-Foror N-Bocsubstituentsatthetwoaminogroups,havebeenincorporatedintothepotentchemotacticagent fMLF-OMeinplaceoftheN-terminalnative(S)-methioninetogivetheanalogues 17a–19a and 17b–19b. Thenewligandshavebeenexaminedfortheiractivity(chemotaxis,superoxideanionproductionand lysozymerelease)onhumanneutrophilsasagonistsandantagonists.Compounds 19a and 19b,bearing two N-Forgroupsattheprolinescaffold,areactiveandselectivechemoattractants.Theligand 18b,con- taining N-Foratthe4-aminogroupofthe N-Boc-tAmpresidue,exhibitssignificantchemotacticantago- nism.TheinfluenceofthedifferentsubstitutionattheN-terminalpositionofthenewanaloguesis discussed.