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Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine-containing fMLF analogs

Authors :
Zecchini, G. Pagani
Nalli, M.
Mollica, A.
Lucente, G.
Paradisi, M. Paglialunga
Spisani, S.
Source :
The Journal of Peptide Research; June 2002, Vol. 59 Issue: 6 p283-291, 9p
Publication Year :
2002

Abstract

In order to explore the properties of chemotactic N-formylpeptides containing isopeptide bonds within their backbones, a group of lysine-containing analogs of the prototypical chemotactic tripeptide N-formylmethionyl-leucyl-phenylalanine (fMLF) was synthesized. The new analogs were designed by adding to the HCO-Met or Boc-Met residue a dipeptide fragment made up of Lys and Phe residues joined through Lys N<SUP>α</SUP> or N<SUP>ε</SUP> bonds, in all possible combinations. Thus, the following six pairs of tripeptides were synthesized and examined for their bioactivity: RCO-Met-Lys(Z)-Phe-OMe (2a, b), RCO-Met-Lys(Z-Phe)-OMe (3a, b), Z-Lys(RCO-Met)-Phe-OMe (4a, b), Z-Phe-Lys(RCO-Met)-OMe (5a, b), RCO-Met-Phe-Lys(Z)-OMe (6a, b) and Z-Lys(RCO-Met-Phe)-OMe (7a, b), with R=OC(CH<SUB>3</SUB>)<SUB>3</SUB> and R=H for compounds a and b, respectively. All the new models were characterized fully and their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils determined as agonists (compounds b) and antagonists (compounds a). All N-formyl derivatives 2b-7b are less potent than fMLF-OMe as chemoattractants, but compound 7b exhibits selective activity as superoxide anion producer. Derivatives 2a-7a do not show antagonistic activity towards fMLF induced chemotaxis and O<SUB>2</SUB><SUP>-</SUP> production, however, all these compounds except 4a antagonize lysozyme release by 60%.</BR>

Details

Language :
English
ISSN :
1397002X and 13993011
Volume :
59
Issue :
6
Database :
Supplemental Index
Journal :
The Journal of Peptide Research
Publication Type :
Periodical
Accession number :
ejs4238419
Full Text :
https://doi.org/10.1034/j.1399-3011.2002.02999.x