Studies on the formation of coordination isomers in the copper(II) and nickel(II) complexes of peptides containing histidyl residues

Copper(II) and nickel(II) complexes of an octapeptide (Ac-MKHMGTHS-NH2) and its N-terminally lengthened derivatives (Ac-GGMKHMGTHS-NH2 and Ac-GDMKHMGTHS-NH2) have been studied by potentiometric and spectroscopic measurements. The amino acid sequences of the peptides correspond to the metal binding domains of 96H and 111H residues in the native prion fragments (GT96HS and MK111HM) but these domains are in the opposite order in the model peptides. The results revealed that both histidyl moieties can be effective metal binding sites. Evaluation of CD spectra made it possible to assess the ratio of coordination isomers of mononuclear complexes. The preference both for copper(II) and nickel(II) binding at the GTHS site was obtained in all cases. In the case of nickel(II) this is in a good agreement with the previous results reported for the prion fragments but the opposite distribution was obtained for copper(II). These data strongly support that nickel(II) prefers the binding to the specific sites of peptides best suited for square planar coordination, while the overall stability of copper(II) peptide complexes is finely tuned by the secondary effects of distant side chains. Moreover, the formation of heteropolynuclear copper(II)–nickel(II)–peptide complexes has also been detected and it was found that the addition of nickel(II) to the mononuclear copper(II) species can redistribute the coordination of copper(II) among the available metal binding sites.

The addition of nickel(II) to a mononuclear copper(II) complex of the octapeptide Ac-MKHMGTHS-NH2 will not substitute copper(II) but partially redistribute its binding among the available binding sites.Figure optionsDownload as PowerPoint slide