Zinc(II) binding ability of tri-, tetra- and penta-peptides containing two or three histidyl residues.

Macroscopic and microscopic protonation processes and zinc(II) complexes of a series of multihistidine peptides (Ac-HGH-OH, Ac-HGH-NHMe, Ac-HHGH-OH, Ac-HHGH-NHMe, Ac-HVGDH-NH(2), Ac-HHVGD-NH(2), Ac-HVHAH-NH(2), Ac-HAHVH-NH(2), Ac-HPHAH-NH(2) and Ac-HAHPH-NH(2)) were studied by potentiometric, NMR and ESI-MS spectroscopic techniques. Protonations of histidyl imidazole-N donor functions were not much affected by the number and location of histidyl residues, but the presence of C-terminal carboxylate groups had a significant impact on the basicities of the neighbouring histidyl sites. The formation of 2N(im) and 3N(im) macrochelates with the stoichiometry of [ZnL] was the major process in the complexation reactions of all peptides followed by the formation of hydroxo or amide bonded species. Thermodynamic stabilities of the zinc(II) complexes were primarily determined by the number of histidyl residues, but the presence of C-terminal carboxylate functions has also a significant contribution to metal binding. The stabilizing effect of the aspartyl beta-carboxylate group was also observed, but its extent is much weaker than that of the C-terminal carboxylate with a neighbouring histidyl residue. Zinc(II) promoted peptide amide deprotonation and co-ordination was observed only in the zinc(II)-Ac-HHVGD-NH(2) system above pH 8.