Projects / Molecular structures to targeting tumor cells

Cyclopeptides as chelating agents

Profiles

European Institute of Oncology

We are also involved in the synthesis and characterization of constrained cyclopeptides bearing various side chains on the core nucleus. It is well known that His-containing peptides play an important role in copper complexation. The His-Xaa-His-Xbb motif is of straightforward importance for the synthesis of diagnostic and therapeutic copper binding peptides mimicking the binding site of metalloproteins. The copper complexation abilities were studied for all peptides with different techniques: electrochemistry, UV-Vis spectroscopy, mass spectrometry, and circular dichroism. Recently, we discovered that the cyclopeptide c(Lys-dHis-βAla-His) (DK13) strongly promoted dioxygen oxidation of the DK13/Cu(II) to Cu(III) complex. In order to clarify the structure of DK13/Cu(III) complex, EXAFS and XANES study was performed at the Grenoble European Synchrotron Radiation Facility. At the same time were studied the complexes of the  c(Lys-His-βAla-His) (LK13)/Cu(II) and  of c(Gly-βAla-Gly-Lys) (GK13)/Cu(II). The spectral data obtained showed that this latter contained only copper(II) ions while the diastereoisomer LK13 was a mixture of Cu(II) and Cu(III) species. The different behaviour of the three cyclotetrapeptides strongly suggested ancillary involvement of the imidazole side chains in the complex formation.

 

A. Pratesi, P. Zanello, G. Giorgi, L. Messori, F. Laschi, A. Casini, M. Corsini, C. Gabbiani, M. Orfei, C. Rosani, M. Ginanneschi ‘New Copper(II)/Cyclic Tetrapeptide System That Easily Oxidizes to Copper(III) under Atmospheric Oxygen’ Inorg. Chem., 2007, 461, 10038-10040.

 

A. Pratesi,G. Giuli, M.R. Cicconi, S. Della Longa, T.C. Weng, Mauro Ginanneschi‘Dioxygen Oxidation Cu(II)→Cu(III) in the Copper Complex of cyclo(Lys-DHis-βAla-His): a Case Study by EXAFS and XANES Approach’ Accepted for publication in Inorganic Chemistry.