The role of the histidine residue in the coordination abilities of peptides with a multi-histidine sequence towards copper(II) ions

Cu2+ complexes with peptides containing three histidine residues have very specific metal binding abilities and can mimic the structures of various multi-histidine metal binding sites in proteins. The main goal of the work concerns the investigations of coordination abilities of the group of N-terminally protected Ac-His-Arg-His-Gly-His-Gly, Ac-His-Gly-His-Arg-His-Gly, Ac-Gly-His-His-Arg-His-Gly and Ac-His-His-Gly-His-Arg-Gly, and their unprotected analogs His-Arg-His-Gly-His-Gly, His-Gly-His-Arg-His-Gly, Gly-His-His-Arg-His-Gly and His-His-Gly-His-Arg-Gly towards Cu2+ ions. Detailed spectroscopic (UV/Vis, CD and EPR) and potentiometric studies have been made. The stoichiometry and binding mode for each ligand-Cu2+ system were determined. In the case of N-terminally protected peptides the coordination begins at the imidazole nitrogen(s) which act as the anchoring groups. At physiological pH the {3N(im), 2N(-)} binding pattern is suggested and at high pH three amide nitrogens are involved in Cu2+ binding. According to the coordination abilities of the unprotected peptides, the position of the histidine residue determines the coordination mode. For His(1) peptides the histamine-like {NH2, N-im} mode for the first species is suggested. The final albumin-like coordination mode is proposed not only for HGHRHG and HRHGHG but also for GHHRHG. For ligands with the His-Xaa-His motif the {2N(-), 2N(im)} binding mode is formed easier. For ligands with His(2) the 3N complex with the {NH2, N-, N-im} binding pattern is a dominant species within the physiological pH range. The protection of the amine group caused a significant decrease of the coordination abilities of the peptides. (C) 2008 Elsevier Ltd. All rights reserved.