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

Abstract

A linear decapeptide containing three His and one Asp residues and a β-turn-inducing dProPro unit was synthesised. A detailed potentiometric, mass spectrometric and spectroscopic study showed that at a 1:1 ratio of CCu /Cpeptide this peptide formed a major [CuH(O(dPro)-Asp)](2+) species (pH range 5.5-7.0), in which the Cu(2+) ion was bound to the His and Asp residues in square-planar or square-pyramidal geometries. The stability constant corrected for protonated species (log K* CuH(O dPro-Asp)=9.33) is almost equal to the value obtained for the parent [CuH(OAsp)](2+) species (log K*CuH(O-Asp) =9.28), but lower than that obtained for the cyclic [CuH(C-Asp)](2+) complex (log K*CuH(C-Asp) =10.79) previously published. Thus, the replacement of the ProGly unit by the stronger β-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 Keff showed that this peptide behaved similarly to the O-Asp or C-Asp counterparts, depending on the pH value. The cyclic voltammetry data indicated that the most easily reducible species were [CuH(O-Asp)](2+) (E'(0) =262 mV versus a normal hydrogen electrode (NHE)) and [CuH(O(dPro)-Asp)](2+) (E'(0) =294 mV versus NHE) complexes, the peptidic scaffolds of which are open. A lower value was obtained for [CuH(C-Asp)](2+) (E'(0) =24 mV 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.

The Analysis of Cu(II)/Zn(II) Cyclopeptide System as Potential Cu,ZnSOD Mimic Center

“…Several authors have brought the attention to the redox properties (Fragoso et al 2015 ) as well as antioxidant/superoxide scavenging of Cu(II) complexes (Fragoso et al 2015 ; Pap et al 2011 ). The copper (II) complexes exhibit antioxidant properties due to their capacity to mimic the activity of the superoxide dismutase enzyme.…”

Constant-pH MD Simulations Portray the Protonation and Structural Behavior of Four Decapeptides Designed to Coordinate Cu2+

“…Recently, the group has also studied the effect of replacing the ProGly unit in the O-Asp peptide by the stronger β-turn inducer dProPro unit (O dPro -Asp). 20 For each of the four peptides containing the ProGly unit, at neutral or near neutral pH and 1:1 proportion of Cu 2+ and peptide, it is observed that there is formation of a main coordination species that seems to bind a single copper through the three neutral imidazoles and, when present, the charged Asp side chain. 18,19 The spectroscopic results are consistent with a distorted square-planar or square pyramidal geometry for coordination, where the remaining coordination sites would be occupied by water molecules.…”

“…The structures of these four peptides are depicted in Figure . Recently, the group has also studied the effect of replacing the ProGly unit in the O-Asp peptide by the stronger β-turn inducer dProPro unit (O dPro -Asp) …”

Exploring the Specificity of Rationally Designed Peptides Reconstituted from the Cell-Free Extract of Deinococcus radiodurans toward Mn(II) and Cu(II)

“…Furthermore, several Cu(II)–peptide complexes, in particular those containing histidine residues, demonstrated antioxidant properties. 17 − 21 For example, the tripeptide Gly-His-Lys, a naturally occurring component of the plasma and liver cell growth factor, in complex with Cu(II) demonstrated to possess a SOD-mimetic activity, and a simple modification of the peptide sequence, to His-Gly-Lys increased its activity ≤223-fold. 22 , 23 Likewise, the complex of Cu(II) with the first four amino acids of the N-terminus of human albumin Asp-Ala-His-Lys exhibited SOD-like activity by significantly inhibiting superoxide formation.…”