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Speciation 98: Abstracts
Elzbieta Lodyga-Chruscinska,1 Giovanni Micera2, Daniele Sanna2, Jacek Olczak3, Janusz Zabrocki3, L. Chruscinski4
1 Institute of General Food Chemistry, Technical University
of Lodz, Lodz, Poland;
2 Department of Chemistry, University of Sassari, Sassari,
Italy;
3 c Institute of Organic Chemistry, Technical University
of Lodz, Lodz, Poland;
4 Faculty of Process & Environmental Engineering,
Technical University of Lodz, Poland
In the pharmacology of opioid peptides, the selectivity toward the specific receptors is of the greatest importance and it depends from the structure of the peptide.
Metal ions can modify the conformation of bioactive peptides and affect their activity. The interaction of metal ions with bioactive ligands is therefore very important, particularly in relation to the pharmacological applications. The concentration of copper(II) is relatively high in the human brain. An interesting and not yet completely understood problem is the effect of copper ions on the modification of the neurohormone activity [1]. Such an influence was suggested with Met-enkephalin and other peptides [2, 3], where Cu(II) imposes a specific conformation, comparable to a b-turn structure.
This study was undertaken to understand the specific interaction of Cu(II) with the enkephalin analogue Tyr-D-Ala-Gly-y[CN4]-Phe-Leu. In this molecule the 1,5-disubstituted tetrazole ring y[CN4] mimics the cis-peptide bond in peptide chains and locks the peptide analogue into a geometry corresponding to the cis isomer [4, 5].
According to our study, performed by pH-potentiometry, CD and EPR, we can suggest that the chelating ability of Tyr-D-Ala-Gly-y(CN4)-Phe-Leu is significantly higher compared to that of unmodified Leu-enkephalin and [D-Ala2]-enkephalin. The y(CN4) ring favours the b-turn in the peptide molecules and strongly affects the coordination to Cu(II). Complexes CuL and CuH-1Lwith 3N and 4N donor sets, respectively, are formed in the physiological pH range. The results substantiate that the metal ion stabilizes the b-turn structure of the peptide and likely influences the bioactivity of the molecule.
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