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 {3Nim, 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 His1 peptides the histamine-like {NH2, Nim} 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−, 2Nim} binding mode is formed easier.For ligands with His2 the 3N complex with the {NH2, N−, Nim} 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.

Graphical abstractThe coordination of the group of protected and unprotected peptides containing three histidyl residues in the sequence were investigated towards Cu2+ ions. The investigations were performed by potentiometric, spectroscopic and computer calculations. Obtained results have determined a number of different binding modes strictly depending on position of histidyl residue.Figure optionsDownload full-size imageDownload as PowerPoint slide