Design, Synthesis And Structure Analysis Of Tumor-associated Carbohydrate Antigen Glycopeptide Derivatives

The research of synthetic tumor therapy vaccines with tumor-associated carbohydrate antigens has made great progress in the last few years. Vaccine is constituted by tumor-associated carbohydrate antigens and immunity stimulant (peptides and protein). After injecting vaccine into the patients, the vaccine will accelerate immune system to produce special antibodies and T-cell involved special immune response to kill tumor cells. Generally, vaccine has three sections : tumor-associated carbohydrate antigen, linker(with or without) and immunity stimulant (peptides or protein).Due to the reported high immune activity of glycopeptides derived from tumor-associated carbohydrate antigens, we design a glycopeptides libraries which is constituted by the single sugar of the natural immune polysaccharide (such as glucose, Galactose, galactosamine, mannose, arabinose, ribose, rhamnose) and immune peptides(such as Leu-Leu -Tyr(LLY), Tyr-Gly(YG), Tyr-Gly-Gly(YGG), Gly-Leu-Phe (GLF), Leu-Leu -Phe(LLF), Leu-Gly-Tyr(LGY)) through serine or threonine.1. By exploring the synthetic methodology of glycopeptides, we established the synthesis conditions of protection, coupling and deprotection in solution-phase combinatorial synthesis. The general method for glycopeptides synthesis in solution-phase combinatorial synthesis was also confirmed.2. The experimental conditions of monosaccharide methylation, demethylation and activation were optimized to improve the yield of productions. Also, the separation of activated α.β configuration molecules and the debenzylation conditions were acquire.3. It was identified that turnning-ester method was not suitable to synthesizing the Fmoc-Ser-Bu~t, Fmoc-Thr-Bu~t. Accordinging to references, we synthesized Fmoc-Ser-Bu~t, Fmoc-Thr-Bu~t. By protecting side phenol hydroxyl with benzyl, the...