Studies Directed Towards the Synthesis of Immunologically Relevant Carbohydrates

Tumor cells often express an over abundance of unique carbohydrate structures. It is believed that vaccines targeting these structures could elicit an immune response capable of degrading tumors and eliminating micrometastases. Paramount to this endeavor is the ability to design and synthesize vaccines that can induce an immune response against carbohydrates. This is often difficult for a number of reasons, including: (i) the inherent low immunogenicity of carbohydrates, (ii) challenges associated with isolating and purifying large quantities of naturally occurring polysaccharides to homogeneity, and (iii) the challenges presented by complex carbohydrate synthesis.
This study focuses on the α-Gal epitope, a unique, highly immunogenic carbohydrate that, once incorporated into a vaccine, has the potential ability to stimulate an immune response against a structurally linked tumor-associated carbohydrate antigen. Studies directed towards a one-pot synthesis of the α-Gal epitope were carried out with unsatisfying results. The underlying reasons for the difficulty of this synthesis were elucidated. This led to the development of a Fmoc-based strategy of oligosaccharide synthesis that afforded the pure α-Gal epitope in high overall yield. The synthesized α-Gal epitope derivative was converted into a glycoamino acid and initial studies on the synthesis of a glycopeptide-based antitumor vaccine were performed.