title: 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.
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras (Portugal).
authors.forename: Ana
authors.initials: A
authors.lastname: Fragoso
authors.affiliation: Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France).
authors.forename: Tiago
authors.initials: T
authors.lastname: Carvalho
authors.affiliation: Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France).
authors.forename: Pierre
authors.initials: P
authors.lastname: Rousselot-Pailley
authors.affiliation: Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001, Lisboa (Portugal).
authors.forename: Margarida M
authors.initials: MM
authors.lastname: Correia Dos Santos
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras (Portugal).
authors.forename: Rita
authors.initials: R
authors.lastname: Delgado
authors.affiliation: Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France). olga.iranzo@univ-amu.fr.
authors.forename: Olga
authors.initials: O
authors.lastname: Iranzo
mesh_terms: D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D010455:Peptides; D006639:Histidine; D003300:Copper
keywords: copper; peptides; redox chemistry; speciation; structure-activity relationships