Master of Science
Dr. Leonard Luyt
Protein secondary structure can be mimicked by incorporating structural constraints into peptides and this can be facilitated by metal coordination. The objective of this project is to establish a chelation system with a cancer targeting peptide sequence, where the coordination to a metal centre results in a cyclic metallopeptide. Cyclic RGD peptides are antagonists for αvβ3 and other integrins, which are present during tumour angiogenesis. Arg-Gly-Asp (RGD) sequence is employed in the peptide backbone, with an un-natural amino acid (3-Pal) and a chelating molecule (pyridyl-triazole, pyta) present on opposite ends of the peptide sequence to form a linear peptide sequence, pyta-RGD-3-Pal-NH2. The linear peptide was reacted with [Re(OH2)3(CO)3]+ to form a cyclic system, with the pyridyl-triazole coordinating in a bidentate fashion. The linear peptide and resulting cyclic metallopeptide were characterized by high resolution mass spectrometry (HRMS), Circular Dichroism (CD) spectroscopy, one- and two-dimensional 1H-NMR spectroscopy, variable temperature (VT) NMR spectroscopy, with purity > 90% as determined by HPLC. Computational studies on the coordinated peptide suggested intra-molecular hydrogen bonging that were consistent with VT NMR data. The linear peptide was successfully radiolabelled with Tc-99m demonstrating the potential application as a SPECT imaging agent for angiogenesis. This approach to adding a structural constraint, through metal-based peptide cyclization, results in a metallopeptide where the metal is central to creating the turn mimetic.
Patel, Aagam, "The Development of Cyclic RGD Peptides Stabilized Through 99mTc/Re(CO)3+" (2015). Electronic Thesis and Dissertation Repository. 3207.