Katyonik antibakteriyel peptitlerin sentezi

When a tissue is damaged, inflammations, biological response of the body to the injury, is maintained to repair the area. Tissues are regenerated by a chemical network system and then inflammation is removed after repair completed. However, when tissue cells continue to proliferate in an inflammation rich environment, tumor cells evolve from inflammatory cells. As the relationship between inflammation and tumor progression becoming clear, it is crucial to distinguish inflammation from infections by means of early diagnosis of cancer. For this matter, cationic antibacterial peptides can be useful as they accumulate at infection but not inflammations. Surgery, radiotherapy and chemotherapy are the main treatments of cancer. In the early stage of cancer, surgery is the standard application used for either therapy or diagnosis. Besides the constantly improving treatment strategies, new diagnostic agents are needed to be explored. In case of early detection and diagnosis, it is important to utilize proteins that are formed around tumor microenvironment as biomarkers. Specific proteins and its ligands are chosen as they are the basis of the tumor microenvironment formation that consequently provides tumor generation and development. The recent technology named molecular imaging can be used in monitoring these molecular imaging agents. The aim of this thesis is to develop new imaging agents for the detection of infections and imaging of tumors at the cellular and molecular levels. Thus, labeled peptides and peptidomimetics that are able to bind with high affinity and selectivity to bacteria membranes and to biomarkers expressed by immune and stromal cells of tumors respectively were designed and produced. In the scope of this study, molecules were designed with pharmacophore approach. More than one antibacterial peptide sequences were synthesized and then Rhodamine B, which is an antibacterial imaging agent was added. The aim of this project is to use these dye-labeled peptides as molecular contrast agents. As a result of the experiments, antibacterial peptide dye fixation was successfully carried out and the analysis proved that the result was correct. Additionally, organic molecules as fragments of various peptidomimetic structures were synthesized, they were purified and characterized. After laboratory studies are completed biomarker affinity and stability analyses will be performed. According to the obtained results from these studies, modifications and alterations will be applied to improve performance. Once the biologically active compounds have been identified, they will be conjugated with DOTA-chelates radio-labeling with Ga68 for PET-CT imaging.