The rational design of peptide-based PET-ligands against the hFRα target protein

Today, rapid and accurate diagnosis of many diseases is of great importance in terms of choosing appropriate treatment methods and avoiding the loss valuable time. For many cancer types, it is possible to detect suitable biomarkers by using both scientific literature and bioinformatics databases. It has been found that the Human Folic Acid Receptor α (hFRα) protein is over expressed in many cancers. Therefore, it is accepted that hFRα can act as a biomarker protein in cancer imaging. Positron Emission Tomography-Computed Tomography (PET-CT), which is of great importance among the methods used for the diagnosis of cancer disease by making use of oncological imaging methods, provides detailed information about the tumor tissues hidden in our body by displaying the metabolic and functional states of organs and tissues within the framework of anatomical information. The most important disadvantage is that it brings serious limitations due to the scarcity of agents that can mark pathological areas in a specific and sensitive way. As a result, it makes it difficult to follow the differences between the detection and treatment stages of cancer. In this thesis, new peptide-based PET-Ligands were developed as an alternative to excisting PET agents that can bind with high selectivity and affinity to specific biomarkers of immune and stromal cells, especially in the tumor microenvironment. In our preliminary studies, 16 peptide-based PET-Ligands, which were predicted to bind to hFRα, were designed using molecular modeling techniques. Afterwards, the possible binding affinity and dynamic binding relationships of these peptides with the hFRα target protein were investigated. In the light of this information, 12 new peptides were designed and suggested for synthesis.