Drastic Effect of the Peptide Sequence on the Copper‐Binding Properties of Tripeptides and the Electrochemical Behaviour of Their Copper(II) Complexes

Abstract

The binding and electrochemical properties of the complexes Cu -HAH, Cu -HWH, Cu -Ac-HWH, Cu -HHW, and Cu -WHH have been studied by using NMR and UV/Vis spectroscopies, CV, and density functional calculations. The results obtained highlight the importance of the peptidic sequence on the coordination properties and, consequently, on the redox properties of their Cu complexes. For Cu -HAH and Cu -HWH, no cathodic processes are observed up to -1.2 V; that is, the complexes exhibit very high stability towards copper reduction. This behaviour is associated with the formation of very stable square-planar (5,5,6)-membered chelate rings (ATCUN motif), which enclose two deprotonated amides. In contrast, for non-ATCUN Cu -Ac-HWH, Cu -HHW complexes, simulations seem to indicate that only one deprotonated amide is enclosed in the coordination sphere. In these cases, the main electrochemical feature is a reductive irreversible one electron-transfer process from Cu to Cu , accompanied with structural changes of the metal coordination sphere and reprotonation of the amide. Finally, for Cu -WHH, two major species have been detected: one at low pH (<5), with no deprotonated amides, and another one at high pH (>10) with an ATCUN motif, both species coexisting at intermediate pH. The present study shows that the use of CV, using glassy carbon as a working electrode, is an ideal and rapid tool for the determination of the redox properties of Cu metallopeptides.

Triggering Cu-coordination change in Cu(ii)-Ala-His-His by external ligands

“…This includes their spectroscopic properties, correlated with one different donor atom. 14,15 The time scales of Cu(II) self-exchange reactions are dramatically different: they are slow for XZH (minutes) but fast for XH (< seconds). 16 With respect to redox properties, Cu(II) coordinated to XZH can be oxidized to Cu(III) while Cu(II) in a Cu(XH) complex can be reduced to Cu(I) in the [-1.0,+1.0 V/vs SCE range].…”

Peptidic Scaffolds To Reduce the Interaction of Cu(II) Ions with β-Amyloid Protein

“…Interestingly, the addition of Cu-Aβ(1-16) to C-Asp produced the partial quenching of the emission of the free C-Asp peptide. The other peptides displayed the same emission intensity before and after adding 1 equivalent of Cu-Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). This suggests that C-Asp either rapidly coordinates Aβ-bound Cu producing a ternary species, or the peptide is capable of removing Cu(II) from the Cu-Aβ(1-16) complex.…”

“…After incubation for 4 hours at 37 ºC (Fig. S3), the copper-induced quenching increased for all peptides, even when treated with Cu-Aβ (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). This observation illustrates the importance of kinetics regarding these interactions and reveals a dynamic copper exchange between the decapeptides and Aβ(1-16), whose study is beyond the scope of this work.…”

“…H-Xaa-Xaa-His including H-His-Xaa-His -are particularly effective in redox-silencing Cu(II) through the impediment of its reduction by endogenous reducing agents and the subsequent production of ROS. 13 Both the high binding affinity towards Cu(II) and the stabilization of its oxidation state have been attributed to the involvement of two deprotonated amide nitrogen atoms from the peptide backbone; such deprotonation is favored at medium to high pH values, as it is the case for physiological conditions. The imidazole ring of the His3 residue completes the formation of three fused five-and six-membered chelating rings, leading to a very stable square-planar complex.…”

Self‐assembly of hairpin peptides mediated by Cu(II) ion: Effect of amino acid sequence

“…[10][11][12][13][14][15] Synthetic peptides with different sequences have been used to explore the influence of sequence of amino acids to peptide self-assembly and ion coordination. [16][17][18][19][20][21][22] For example, the number and position of amino acid residues adjacent to alkyl tail could affect the structure and properties of self-assembly. [23,24] According to the previous research results, the isomeric peptide amphiphiles with VVEE and EEVV sequence could facilitate the formation of cylindrical nanofibers, while alternating hydrophobic and hydrophilic amino acids as VEVE and EVEV in peptide amphiphiles induced the formation of flat nanostructures such as nanobelts.…”