Interaction of an Innovative Peptide-Based Drug Candidate with Transition Metal Ions

Abstract

The present thesis investigates the interaction of the antiangiogenic pentapeptide ATN-161 (Ac-PHSCN-NH2) with biologically relevant transition metal ions (Cu(II), Ni(II), Zn(II), and Co(II)) through complex formation and oxidation studies. These studies are driven by the peptide's potential for neuroprotection and anticancer activity, along with the previously unreported impact of metal coordination and oxidative stability on its biological activity. The complex formation process was analysed using pH-potentiometric, UV-Vis and CD spectroscopy. Oxidation studies were conducted using the Cu(II):ATN-161:H2O2 system and monitored by HPLC. The identification of oxidation products was performed by electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) fragmentation analysis. This work contributes to the understanding of the metal ion interactions and oxidative stability of ATN-161, providing a chemical foundation for understanding how these processes may influence its preclinical performance and therapeutic applications.