The Role of the Disulfide Bridge in the Copper (II) Binding by the Cyclic His4-Peptide.

In this paper, we present studies on the influence of the disulfide bridge on the copper (II) ions' binding abilities by the cyclic His4-peptide. The studied ligand HKHPHRHC-S-S-C consists of nine amino acids. The cyclic structure was obtained through a disulfide bridge between two cysteinyl groups. Moreover, this peptide is characterized by the presence of four His residues in the sequence, which makes it an interesting ligand for transition metal ions. The potentiometric and spectroscopic (UV-Vis spectroscopy and circular dichroism spectroscopy (CD)) studies were carried out in various molar ligand to metal ratios: 2:1, 1:1, and 1:2, in the pH range of 2.5-11 at 25 °C. The results showed that the cyclic His4-peptide promotes dinuclear complexes in each of these systems and forms the final dinuclear species with the {NIm, 3N-amide}{NIm, 3N-amide} coordination mode. The obtained data shows that cyclization by the formation of the disulfide bond has an impact on the peptide chain flexibility and appearance of additional potential donors for metal ions and influences the copper (II) ions' coordination.

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 S-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,ß-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)-ß-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.

The Binding Ability of a Bicyclic Somatostatin Analogue Towards Cu(II) Ions.

Somatostatin (SST) analogues have aroused the interest of scientists for years. This group of compounds is used in the diagnosis and treatment of neuroendocrine tumors. However, new molecules useful as radiopharmaceuticals in targeted therapy are still searched for. Bicyclic peptides seem to be very interesting in this context. These molecules are associated with beneficial properties. In this work, we present studies on the binding ability of the bicyclic analogue of somatostatin toward Cu(II) ions which could potentially be a chelator for copper radionuclides. The research is focused on the analysis of Cu(II) interactions with the metal binding cycle of the ligand and the influence of the receptor binding site on the coordination process. This is a novelty in comparison to the SST analogues used in medicine, where a metal ion is coordinated by a chelator and connected with a bioactive molecule by the linker. In this work, we present the first coordination study for a bicyclic ligand. The obtained results showed that the complexes with only imidazole donors are characterized by significantly higher stability in comparison to the other peptides.