Synthesis and biological evaluation of new active For‐Met‐Leu‐Phe‐OMe analogues containing para‐substituted Phe residues |
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Authors: | Adriano Mollica Federica Feliciani Azzurra Stefanucci Roberto Costante Gino Lucente Francesco Pinnen Daniela Notaristefano Susanna Spisani |
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Affiliation: | 1. Dipartimento di Scienze del Farmaco, Università di Chieti‐Pescara “G. d'Annunzio”, , 66100 Chieti, Italy;2. Istituto di Chimica Biomolecolare (CNR) c/o Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza”, Università di Roma, , 00185 Roma, Italy;3. Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, , 44121 Ferrara, Italy |
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Abstract: | In the present study, we report synthesis and biological evaluation of the N‐Boc‐protected tripeptides 4a–l and N‐For protected tripeptides 5a–l as new For‐Met‐Leu‐Phe‐OMe (fMLF‐OMe) analogues. All the new ligands are characterized by the C‐terminal Phe residue variously substituted at position 4 of the aromatic ring. The agonism of 5a–l and the antagonism of 4a–l (chemotaxis, superoxide anion production, lysozyme release as well as receptor binding affinity) have been examined on human neutrophils. No synthesized compounds has higher activity than the standard fMLF‐OMe tripeptide to stimulate chemotaxis, although compounds 5a and 5c with ‐CH3 and ‐C(CH3)3, respectively, in position 4 on the aromatic ring, are better than the standard tripeptide to stimulate the production of superoxide anion, in higher concentration. Compounds 4f and 4i , containing ‐F and ‐I in position 4, respectively, on the aromatic ring of phenylalanine, exhibit significant chemotactic antagonism. The influence of the different substitution at the position 4 on the aromatic ring of phenylalanine is discussed. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd. |
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Keywords: | biological activity chemotaxis receptor binding human neutrophils fMLF‐OMe analogues peptidomimetics |
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