Coordination properties of selected cyclic peptide hormones and their analogues

Hormones are a heterogeneous, significant compounds, responsible for proper functioning of living organisms, produced by specialized cells, tissues and glands. Theirs main role is signals transmission to target tissues, responsible for the right working of the whole organism. Dysfunctions of the hormones homeostasis balance lead to disease states [1-3]. Recently, scientists have paid attention to role of the metal ions in the proper synthesis of these compounds and functioning of human body [4]. More and more scientific works explain the complicated roles of metals as beneficial factors that stimulate the conformation of peptides. Metal ions are responsible for biological properties and influence of hormones binding to appropriate receptors, but also adverse factors [4,5]. The search for an answer to the question about the metal - hormone relationship has led to the development of a new, interdisciplinary studies: metalloendocrinology, linking inorganic chemistry with endocrinology [4]. In this work, we present the literature data that relate to metal - peptide hormone interactions. We focused on cyclic hormones with a disulfide bridge and their analogues. In our review we have focused on selected natural cyclic peptide hormones: oxytocin, vasopressin, somatostatin, hepcidin and amylin. The studies on the coordination abilities showed that transition metal ions, such as copper(II), zinc(II) or nickel(II), form stable complexes with described peptides. Metal ions actively participate in many phenomena. They have played role in the formation of amylin aggregates in patients with type 2 diabetes [6]. The high ability to copper(II) by hepcidin may have an effect on its homeostasis [7]. Stable complexes of oxytocin and vasopressin facilitate binding with appropriate receptors for these peptides [8]

Detailed Insight into the Interaction of Bicyclic Somatostatin Analogue with Cu(II) Ions

Somatostatin analogues are useful pharmaceuticals in peptide receptor radionuclide therapy. In previous studies, we analyzed a new bicyclic somatostatin analogue (BCS) in connection with Cu(II) ions. Two characteristic sites were present in the peptide chain: the receptor- and the metal-binding site. We have already shown that this ligand can form very stable imidazole complexes with the metal ion. In this work, our aim was to characterize the intramolecular interaction that occurs in the peptide molecule. Therefore, we analyzed the coordination abilities of two cyclic ligands, i.e., P1 only with the metal binding site and P2 with both sites, but without the disulfide bond. Furthermore, we used magnetic circular dichroism (MCD) spectroscopy to better understand the coordination process. We applied this method to analyze spectra of P1, P2, and BCS, which we have described previously. Additionally, we analyzed the MCD spectra of P3 ligand, which has only the receptor binding site in its structure. We have unequivocally shown that the presence of the Phe-Trp-Lys-Thr motif and the disulfide bond significantly increases the metal binding efficiency