| title: | Novel peptidic and non-peptidic antioxidative predrugs, their biochemical-molecular characterisation and testing on different model systems |
|---|---|
| reg no: | ETF6503 |
| project type: | Estonian Science Foundation research grant |
| status: | accepted |
| institution: | University of Tartu |
| head of project: | Ursel Soomets |
| duration: | 01.01.2005 - 31.12.2008 |
| description: | This project is continuing previous investigation (supported by Estonian Scientific Foundation; Grant 4913). Our group designed and synthesized novel glutathione (GSH) analogue, in which to the N-terminus of GSH molecule methoxyphenylalanine residue was added. (Patent: Antioxidant, inventors: Ü. Langel, U. Soomets, E. Vasar, M. Zilmer, assignee : Vulpes Ltd., no. 110035500. PCT/SE01/01351).The main aims of the study. 1. Design, synthesis and in vitro testing, including characterisation of antioxidative properties, of novel peptidic and non-peptidic compounds. Addition of hydrophobic coded and non-coded amino acid residues to the N-terminus of GSH; to amidate or esterify C-terminal carboxylic acid group of analogues. 2. Synthesis of radioactively labeled (tritium label) UPF analogues; synthesis of fluorescence labeled UPF analogues; synthesis of cell-penetrating UPF analogue constructs (UPF-S-S-cell-penetrating peptide). To study cellular internalisation and intracellular distribution of novel compounds in different cell lines: Bowes melanoma cell line, primary neuronal cell cultures (astrocytes), and in pancreatic beeta-cells. 3. To study toxicity of novel UPF analogues in different cell (Bowes cells, PC12, SHSY-5Y cell lines, primary neuronal cultures). 4. To study interaction of novel UPF analogues with different proteins in the blood, in cellular membranes and in cytoplasm. 5. To study possible preventive effects of novel UPF analogues in Parkinson disease MPTP model and in the model of nephrectomy. |
| project group | ||||
|---|---|---|---|---|
| no | name | institution | position | |
| 1. | Kersti Ehrlich | University of Tartu | specialist | |
| 2. | Riina Mahlapuu | University of Tartu | researcher | |
| 3. | Priit Põder | Kardiovaskulaarkirurgia kliinik TÜ | resident in vascular surgery field and PhD student | |
| 4. | Kristiina Roots | University of Tartu | PhD student | |
| 5. | Ursel Soomets | University of Tartu | Associate Professor | |
| 6. | Säde Viirlaid | University of Tartu | lecturer | |