Thesis supervisor: Csilla Kállay
Location of studies (in Hungarian): Debreceni Egyetem, Szervetlen és Analitikai Kémiai Tanszék Kémiai Épület, IV. emelet, D428, D408, D411, D429, D430 Abbreviation of location of studies: D428
Description of the research topic:
The development of different neurodegenerative disorders is related to the abnormal processing of proteins in the brain. Prion and amyloid-β proteins are probably the best known and most studied macromolecules in connection with neurodegeneration. Up to now, there is no common explanation for the development of these diseases but specific conformational changes, oxidative or hydrolytic cleavage leading to the formation of protein aggregates are believed to be the most common starting points. These processes are associated with the involvement of metal ions, especially copper(II) ions. Therefore the role of metal ions in the development of degenerative diseases is in the focus of bioinorganic researches.
The interaction between metal ions and peptides can be important in two areas:
1) The coordination of the metal ion to the peptide.
Coordination of metal ions by the amino acid side chains of proteins is an extensively studied research area. The study of the interaction of biologically important prion proteins and amyloid-β peptides with various transition metal ions started in our research group 20 years ago.
2) Metal ion-catalysed oxidation of the peptide.
Recent studies have shown that oxidative stress and reactive oxygen species formation also contribute to the development of neurodegenerative diseases. Studies in this field have started 10 years ago in our research group.
One possible way to understand these very complicated metal ion–protein interactions is the study of the reactions (coordination and oxidation) of the peptide fragments of proteins in the presence of metal ions. Our studies may help to determine the factors which influence the oxidation of proteins, and can contribute to the understanding of the potential role of trace metal ions in these processes. Our aim is to explore how the position of certain amino acids in the peptide chain and their coordination to metal ions affects the oxidation of peptides. The effect of small molecule metal chelators (SMMCs), such as metal-protein attenuating compounds (MPACs) e.g. aroylhydrazones and 'Salan based' ligands will be also studied. These compounds may show protective effect towards the oxidation of the peptides.
We will synthetize the peptides which are not commercially available by solid-phase peptide synthesis. The stability constants of the formed complexes will be determined by pH-potentiometry. UV-Vis and CD and NMR spectroscopy studies will be performed to confirm the structure of the complexes. The progress of oxidation will be monitored by HPLC and the oxidized products will be identified by HPLC-ESI-MS and MS/MS measurements.
Required language skills: angol Recommended language skills (in Hungarian): english Number of students who can be accepted: 1
Deadline for application: 2024-05-15
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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