化學合成癌症相關之醣硫化骨橋蛋白

This thesis aims to study the structure and function roles of sulfation and O-glycosylation on the peptides derived from a tumor-associated protein, osteopontin (OPN), in order to provide a fundamental knowledge for potential cancer vaccine development. Chapter 2 is dedicated to the method development of the synthesis for a library of post-transitionally modified tumor-associated osteopontin peptide antigens, using divergent Fmoc-based solid-phase peptide synthesis (Fmoc-SPPS) with a cassette strategy. Of these synthetic peptides, the one with the highest integrin binding efficiency will be selected as a cancer vaccine candidate. Chapter 3 is devoted to the synthesis of four glyco(sulfo)peptides, each bearing a thrombin cleavable fluorescent tag. For making it easier to synthesis, we performed an on-resin installation of a fluorescent tag: 7-amino-4-aminocoumarylmethyl coumarin (ACC), on the C-terminal of the peptides. The products were used as substrates for the thrombin assay, and we envisioned that such a library would reveal the roles of sulfation and O-glycosylation to the thrombin-osteopontin interactions for the first time. The preliminary results of these peptides against thrombin assay confirmed both tyrosine sulfation and O-glycosylation gave detrimental effects on the thrombin amidolytic activity against synthetic osteopontin peptides.