Glycoproteins are proteins that are post-translationally modified with oligosaccharides. Due to the non-template-mediated biosynthesis of glycoproteins in the nature, glycoproteins always exist as heterogeneous mixtures with different glycan structures. In order to obtain the homogeneous glycoproteins with the well-defined glycan structures for an extensive investigation of the relationship between the structure and function of glycoproteins, synthetic strategies including chemical and chemoenzymatic synthesis have been employed and achieved great success over the past years. Among these approaches, our research group has developed a novel serine/threonine ligation (STL), which involved a chemoselective ligation between a peptide with a salicylaldehyde (SAL) ester at the C-terminus and an N-terminal serine or threonine of another peptide to generate the natural Xxx-Ser/Thr linkage (Xxx represents any amino acid) at the conjugation site. STL provides more possibilities for disconnection sites for convergent protein/glycoprotein synthesis. My research has been focused on the synthesis of MUC1 glycopeptides. MUC1 is a transmemberane glycoprotein expressed on the apical surface of most normal epithelial cells at low levels but highly overexpressed on the entire membrane of human epithelial tumor cells. In the extracellular part, MUC1 contains a variable number of tandem repeat (VNTR) units which consist of twenty amino acids with five potential O-glycosylation sites. As MUC1 has been shown asa promising target for the production of immunostimulating antigens, a variety of chemical assembly strategies have been applied for the development of MUC1 glycopeptide-based anticancer vaccines with high immunogenicity and tumor selectivity, including the construction of multivalent dendrimers presenting tumor-associated MUC1 glycopeptide antigens and the incorporation of various immunoadjuvants. In my studies, I have successfully synthesized the large MUC1 VNTR glycopeptides (40-mer and 80-mer sections) possessing tumor-associated Tn antigens via one and three consecutive STL reactions. On the other hand, the cyclic MUC1 glycopeptide-BSA conjugates has been successfully constructed. We are yet to test the immunological properties of synthetic MUC1 glycopeptide oligomers and MUC1-based glycoconjugates as anticancer vaccine candidates. In addition, inspired by STL, I have developed an aspartic acid ligation, in which a C-terminal peptide-SAL ester chemoselectively reacts with an N-terminal diol group of another peptide under the same conditions as STL to form a six-membered N,O-benzylidene acetal linked intermediate. Followed by treatment with acidsand selectiveoxidation, the natural Xxx-Asplinkage(Xxx represents any amino acid) is chemoselectively generated at the conjugation site. This STL-based aspartic acid ligation has been applied in the synthesis of a series of cyclic and linear peptides. / published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy