Interaction of Cu(II) and Ni(II) with the 63–93 fragment of histone H2B

Chromatin proteins are believed to represent reactive sites for metal ion binding. We have synthesized the 31 amino acid peptide Ac-NSFVNDIFERIAGEASRLAHYNKRSTITSRE-NH₂, corresponding to the 63–93 fragment of the histone H2B and studied its interaction with Cu(II) and Ni(II). Potentiometric and spectroscopic studies (UV-vis, CD, NMR and EPR) showed that histidine 21 acts as an anchoring binding site for the metal ion. Complexation of the studied peptide with Cu(II) starts at pH 4 with the formation of the monodentate species CuH₂L. At physiological pH values, the 3N complex {N_Im, 2N⁻}, CuL is favoured while at basic pH values the 4N {N_Im, 3N⁻} coordination mode is preferred. Ni(II) forms several complexes with the peptide starting from the distorted octahedral NiH₂L at about neutral pH, to a square planar complex where the peptide is bound through a {N_Im, 3N⁻} mode in an equatorial plane at basic pH values. These results could be important in revealing more information about the mechanism of metal induced toxicity and carcinogenesis.