Effect of the Peptidic Scaffold in Copper(II) Coordination and the Redox Properties of Short Histidine-Containing Peptides

A linear decapeptide containing three His and one Asp residues and a -turn-inducing dProPro unit was synthesised. A detailed potentiometric, mass spectrometric and spectroscopic study showed that at a 1:1 ratio of C-Cu/C-peptide this peptide formed a major [CuH(O(dPro)Asp)](2+) species (pH range 5.5-7.0), in which the Cu2+ ion was bound to the His and Asp residues in square-planar or square-pyramidal geometries. The stability constant corrected for protonated species (logK*CuH(OdPro-Asp)=9.33) is almost equal to the value obtained for the parent [CuH(OAsp)](2+) species (logK*(CuH(O-Asp))=9.28), but lower than that obtained for the cyclic [CuH(CAsp)](2+) complex (logK*(CuH(C-Asp))=10.79) previously published. Thus, the replacement of the ProGly unit by the stronger -turn-inducing dProPro unit did not generate a more stable copper(II) species, although the O(dPro)Asp peptide was structured in solution, as shown by circular dichroism (CD) spectroscopy. Interestingly, the calculated value of K-eff showed that this peptide behaved similarly to the OAsp or CAsp counterparts, depending on the pH value. The cyclic voltammetry data indicated that the most easily reducible species were [CuH(OAsp)](2+) (E-0=262mV versus a normal hydrogen electrode (NHE)) and [CuH(O(dPro)Asp)](2+) (E-0=294mV versus NHE) complexes, the peptidic scaffolds of which are open. A lower value was obtained for [CuH(CAsp)](2+) (E-0=24mV versus NHE). A different degree of non-reversibility was observed for the three copper(II) complexes; this could reflect a different degree of flexibility in their respective peptidic scaffolds.