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-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.
Torino
Domenica
D
Dipartimento di Chimica e Tecnologie del Farmaco and Istituto di Chimica Biomolecolare, CNR Sezione di Roma, "Sapienza", Università di Roma, P.le A.Moro, 00185 Roma, Italy.
Mollica
Adriano
A
Pinnen
Francesco
F
Feliciani
Federica
F
Spisani
Susanna
S
Lucente
Gino
G
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D009113:Muramidase / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011392:Proline; D013481:Superoxides
D008024:Ligands; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011392:Proline; D009113:Muramidase