Aleksandra Kotynia

The impact of two –GlyProGly– motifs on formation of di-copper complexes by His4-cyclopeptides

The interactions of copper(II) ions with the macrocyclic peptide, c(HKHGPG)2, were investigated in aqueous solution as a function of pH by potentiometric titration, spectroscopic (UV-Vis, CD, and EPR) and mass spectrometry (ESI-MS) measurements. The experiments were conducted for two different ligand to metal ratios: 1:1 and 1:2. The present study reveals that below pH 6 only mononuclear complexes exist in the case of both systems (L:Cu(II) = 1:1, L:Cu(II) = 1:2). However, in an alkaline medium dinuclear forms are preferred, which are dominant in the system containing two equiv. of copper(II). Under basic conditions the {2NIm, 2Nam−} coordination mode is favored. Furthermore, a molecular modeling study was performed in order to characterize structural aspects of the formation of di-copper(II) complexes by His4-cyclopeptides. The comparison of coordination properties of c(HKHP)2 and c(HKHGPG)2 allowed to characterize the impact of two –GlyProGly– motifs on formation of di-copper complexes by His4-cyclopeptides.

Interactions of anti-Parkinson drug benserazide with Zn(II), Cu(II), Fe(II) ions

One of the treatments of Parkinson disease is based on increasing the brain dopamine level by L-DOPA (LD) applications. To prevent the peripheral degradation of levodopa, another drug, benserazide is applied. On the other hand, during this neurodegenerative disease changes in the homeostasis of metals are observed and the increasing brain zinc levels are postulated to have therapeutic effects. Here we present studies on interactions of Zn(II), Cu(II), Fe(II) ions with benserazide and with benserazide/levodopa in ternary system. By applying mass spectrometry and UV-vis methods we describe the interactions between selected metal ions and the drug additives in the investigated systems. The results show forming of equimolar complexes in the binary and ternary systems.

The unusual coordination abilities of the peptides with βXaaHisGlyHis sequence. The influence of structural modification of the peptide chain on the copper(II) binding

The coordination abilities of tetrapeptides containing beta-amino acids towards Cu(II) ions are presented. The studied tetrapeptides were: Ac-betaAlaHisGlyHis, betaAlaHisGlyHis, Ac-betaAspHisGlyHis, betaAspHisGlyHis, Ac-betaAspHisGly-dHis and betaAspHisGly-dHis. Thorough potentiometric titrations were carried out to establish the stoichiometry of the resulting metal-ligand complexes and the role of free -alphaCOO(-) side chain group in metal binding. The copper(II) coordination mode of the complexes was investigated by performing detailed spectroscopic analyses (UV-Vis, EPR, CD) in strict correlation with potentiometric measurements.

Armed by Asp? C-terminal carboxylate in a Dap-branched peptide and consequences in the binding of CuII and electrocatalytic water oxidation

The imidazole ring of histidine (His) and the methylcarboxylate function of aspartic acid (Asp) are crucial for Cu coordination in enzymes, artificial proteins and other bioinspired systems. In order to elucidate the effect of Asp at the C-terminus, a new branched peptide, H-Gly-Dap(H-Gly)-Asp-NH2 (2GD, Dap = 2,3-diaminopropionic acid) has been synthesized to ligate CuII. While at pH < 8, 2GD favours dimeric complexes at 1 : 1 metal-to-ligand ratio, at increasingly alkaline pH the Asp at the C-terminus creates a {NH2,N−,N−,O−}eq set and the dominance of mononuclear CuLH−2 and CuLH−3 species, according to potentiometry, molecular spectroscopy (UV-visible, circular dichroism and X-band electron paramagnetic resonance) and ESI-MS analysis. The changes in speciation with pH are accompanied by shifts in the CuIII/II redox current peaks that were analyzed by square wave voltammetry (SWV) and allowed the calculation of the pKa values for the CuII and CuIII forms. The 2GD complex exhibits electrocatalytic activity in water oxidation in phosphate buffer. However, when Asp residues are present at all three termini to produce 3D (H-Asp-Dap(H-Asp)-Asp-NH2), the electrocatalysis of water oxidation decreases and, if present only at the N-termini in 2DG (H-Asp-Dap(H-Asp)-Gly-NH2), it ceases. As for CuII ligated by 2GD, a TOF of ∼16 s−1 was calculated at pH = 11 in 0.2 M phosphate electrolyte, which is crucial for catalysis, but also acts as inhibitor anion according to cyclic voltammetry observations. The system is highly tolerant to the presence of chloride, which is a feature of practical importance in efficient water oxidation catalysis.

The Coordination Abilities of Three Novel Analogues of Saliva Peptides: The Influence of Structural Modification on the Copper Binding

Three novel analogues of salivary peptides as sialorphin (QHNPR) and opiorphin (QRFSR) were synthesized by the solid-phase method. The sequences of these ligands were following: AHNPR, QANPR and QRFPR. The aim of our work was investigation in what way some structural modifications may impact on coordination abilities of studied peptides. In this work we presented the interaction of pentapeptides with copper(II) ions in wide range of pH. To determine the coordination model of ligands there were carried out several studies by spectroscopy (UV–Vis, CD) methods and potentiometric measurements.