Peptides complexes with Cu2+ ions as mimetics of superoxide dismutase

Disturbances in the balance between the rates of reactive oxygen species formation and the ability of cells to neutralize them are often cause dysfunction in the human body. Therefore the research on natural antioxidant systems protecting cells against destruction is very important. One of such system acting in human organism is superoxide dismutase (SOD), which is responsible for degradation of the superoxide radical anion into molecular oxygen and hydrogen peroxide. The SOD was discovered in the 40s of the twentieth century, and since then there has been a lot of research on it. Currently, these studies mainly concern searching compounds that may mimic the enzymatic activity of this protein. Groups of these compounds include, for example, peptides, salens, metalloporphyrins or vitamin derivatives. For the proper functioning of the CuZnSOD enzyme necessary is the active center containing metal ions (Rys.2). They mainly coordinate to the nitrogens of the imidazole histidine residues. Due to the fact that peptides may have many histidyl residues in their structure, they could rather than others coordinate with metal ions and they are promising compounds in studies on CuZnSOD mimetics. Therefore we will consider peptide complexes with copper(II) and zinc(II) ions as potential mimetics of superoxide dismutase. In presented review article we have focused on the differences in the coordination manner of divalent copper ions by linear, cyclic and branched peptides. As well as the possibility of creating hetero- and homo-dinuclear complexes are discussed. Moreover we have compared the ability of these complexes to decomposition the superoxide radical with activity of native enzyme

The Unusual Role of Pro in Cu(II) Binding by His2-Cyclopentapeptide

In this paper, we present findings from studying the interaction of copper(II) ions with the His2-cyclopentapeptide and the role of proline used for the purpose of potentiometric titration and UV-Vis, CD and EPR spectroscopic measurements. Experiments of two homodetic peptides differing by one amino acid residue were conducted for a ligand to metal ratio of 1:1 in the pH range 2.5–11.0. The presented studies reveal that peptides form only mononuclear complexes, and the CuH2L complex appears in the system first (for both L1 and L2). Study results show that the presence of Pro influences the structure of formed complexes and their stabilities and has a strong impact on the efficiency of copper(II) coordination

Dipeptides of <i>S</i>-Substituted Dehydrocysteine as Artzyme Building Blocks: Synthesis, Complexing Abilities and Antiproliferative Properties

Background: Dehydropeptides are analogs of peptides containing at least one conjugate double bond between α,β-carbon atoms. Its presence provides unique structural properties and reaction centre for chemical modification. In this study, the series of new class of dipeptides containing S-substituted dehydrocysteine with variety of heterocyclic moieties was prepared. The compounds were designed as the building blocks for the construction of artificial metalloenzymes (artzymes). Therefore, the complexing properties of representative compounds were also evaluated. Furthermore, the acknowledged biological activity of natural dehydropeptides was the reason to extend the study for antiproliferative action of against several cancer cell lines. Methods: The synthetic strategy involves glycyl and phenylalanyl-(Z)-β-bromodehydroalanine as a substrate in one pot addition/elimination reaction of thiols. After deprotection of N-terminal amino group the compounds with triazole ring were tested as complexones for copper(II) ions using potentiometric titration and spectroscopic techniques (UV-Vis, CD, EPR). Finally, the antiproliferative activity was evaluated by sulforhodamine B assay. Results and Conclusions: A simple and efficient procedure for preparation of dipeptides containing S-substituded dehydrocysteine was provided. The peptides containing triazole appeared to be strong complexones of copper(II) ions. Some of the peptides exhibited promising antiproliferative activities against number of cancer cell lines, including cell lines resistant to widely used anticancer agent