Harris, PaulVasetsoi, Nicholas2025-01-072025-01-072024https://hdl.handle.net/2292/70925Cancer continues to be a major leading cause of death worldwide, resulting in millions of deaths each year. While the incidence of cancer has remained relatively stable over the past few decades, the number of individuals diagnosed with cancer continues to rise with the increase in population. Surgery, chemotherapy, and radiation therapy are conventional cancer treatment strategies most used in the modern era; their effectiveness has been well documented in various research papers and displayed globally. However, side effects such as pain, fatigue, anaemia, nerve damage, and hair loss still plague these treatment strategies, being far from flawless and warranting further improvements. Boron neutron capture therapy (BNCT) combines selective uptake of non-radioactive boron 10 (10B) with neutron radiation to target solid malignant tumours. This approach aims to selectively destroy cancer cells while sparing normal cells, potentially reducing the side effects associated with conventional cancer treatments. BNCT utilises FDA-approved boron containing compounds, BSH or BPA, often delivered via nanocarriers to target tumour cells for neutron radiation effectively. A20FMDV2, a 20-amino-acid peptide from the foot-and-mouth disease virus, is highly selective for the αvβ6 integrin. This integrin is a promising therapeutic target due to its high expression in tissue remodelling and neoplastic cells but is normally absence in healthy cells. Despite attempts to use A20FMDV2 as a peptide nanocarrier for BNCT, therapeutic success has been limited by the peptide's poor structural stability, which leads to rapid degradation and cleavage before reaching the target. Research is focused on improving the peptide's scaffold to enhance resistance to peptidases and prevent premature cleavage. Cyclic variants of A20FMDV2 have been developed and showed modest improvements to the structural stability of the peptide. However, a head-to-tail cyclization of A20FMDV2 has yet to be synthesized or studied. Herein, this thesis aims to synthesise a novel, true head-to-tail cyclic A20FMDV2 peptide via Fmoc-SPPS and native chemical ligation (NCL) strategies; furthermore, these techniques will undergo thorough optimisation specifically for the synthesis and NCL of A20FMDV2 to efficiently generate the head-to-tail cyclic peptide with relatively high yield and purity.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmThesisCopyright: the authorAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/