Master of Science
Dr. Leonard Luyt
Peptide-based probes are developed into imaging agents to target two different receptors: receptor for HA mediated motility (RHAMM) and glucagon-like peptide 1 receptor (GLP-1R).
In the first project, peptides are derived from tubulin and mimic HA (hyaluronan), the natural ligand of RHAMM. In order to develop the lead candidate peptides into imaging agents, a DOTA chelator which can coordinate a radiometal was coupled onto the lead peptides. Gallium labelling studies were performed and the labelled probes were used in in vivo mouse studies. Various analogues of two of the candidate peptides were also synthesized using bioisosteric, unnatural as well as natural amino acid replacements. They were incubated with RHAMM-coated magnetic/fluorescent beads and screened using a plate reader. This project resulted in the conclusion that the peptides containing only natural amino acids are not adequate imaging agents, but led to the discovery of novel peptides that have more potential as probes targeting RHAMM in vivo.
In the second project, truncated GLP-1 analogues were synthesized and characterized. The unnatural amino acids, BIP 1 and BIP 2 were first synthesized before being incorporated into the peptides. The potential of the peptides were analyzed by binding assays which determine the IC50 and EC50. The two DOTA chelated peptides were coordinated with 68Ga and in vitro cell studies were performed. Ultimately, this research found an allosteric agonist for the GLP-1R which may have the potential to be a PET imaging probe to monitor type 2 diabetes.
Esarik, Ashley, "The Synthesis and Evaluation of Peptide-Based Probes for the Imaging of RHAMM Expressing Carcinoma and GLP-1R on Pancreatic Beta Cells" (2013). Electronic Thesis and Dissertation Repository. 1637.