Oligosaccharide-protein binding is implicated in several processes including immune related responses, pathogenic invasion and tumor metastasis. Carbohydrate binding inhibitors could lead to therapies for these disease states. Inhibitor development has been slowed by the unavailability of structrually modified complex sugars and continue to be hampered by a lack of detailed understanding of which structural features of the carbohydrate are important and how they affect binding at the molecular level. The studies proposed here focus on the inhibition of protein- carbohydrate recognition to provide both insights into the binding process and a rational approach to develop effective treatments. The system to be probed is the binding of a human breast tumor antigen, globo-H, to monoclonal antibody MBr1. The pioneering work of Prof. Danishefsky at Memorial Sloan-Kettering has allowed access to complex and modified oligosaccharides. Thus, the major advantages of focusing on this system are that both synthetic routes to generate potential inhibitors and assays to evaluate them are in place for rapid advancement toward the research goals.
| Coltart, Don M; Royyuru, Ajay K; Williams, Lawrence J et al. (2002) Principles of mucin architecture: structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains. J Am Chem Soc 124:9833-44 |
| Ragupathi, Govindaswami; Deshpande, Prashant P; Coltart, Don M et al. (2002) Constructing an adenocarcinoma vaccine: immunization of mice with synthetic KH-1 nonasaccharide stimulates anti-KH-1 and anti-Le(y) antibodies. Int J Cancer 99:207-12 |
| Ragupathi, Govindaswami; Coltart, Don M; Williams, Lawrence J et al. (2002) On the power of chemical synthesis: immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines. Proc Natl Acad Sci U S A 99:13699-704 |
