Complex Glycoconjugate Synthesis
Carbohydrate-Based Molecular Recognition
Cell surface carbohydrates, typically conjugated to proteins and lipids, are key elements in the cellular communication that is essential to cellular organization and function in all organisms. Not only do these cell surface constituents mediate normal behavior in cells, but they may also participate in molecular recognition events that are associated with many serious human diseases, including rheumatoid arthritis, viral and bacterial infections, and cancer metastasis. This provides an extremely attractive opportunity for selective chemical intervention of cell function through the targeting of specific cell surface carbohydrate structures.
A central theme of our research is the application of synthetic organic chemistry to the preparation of appropriate carbohydrate structures in order to carry out detailed structural studies addressing their recognition properties. The highly complex structures of carbohydrates, particularly in the form of their corresponding glycoconjugates, often challenge the limits of existing synthetic technology and dictate the development of new methodology. As such, studies addressing biological carbohydrates offer opportunities for discoveries in the both the chemical and biological domains.
One for the focuses of our efforts is the development of synthetic cancer vaccines directed toward cell surface carbohydrate antigen structures. In this context, the synthesis of complex oligosaccharides is currently under investigation, as well as the development of new strategies for the assembly of unnatural glycopeptide structures that may prove useful in the assembly of effective vaccines.
In other studies, we are endeavoring to exploit the dense stereochemical and functional content of carbohydrates to generate new classes of molecules for highly selective biorecognition. In particular, C-glycoside oligosaccharide/peptide hybrids are being examined for specific cell surface and DNA recognition and binding toward the goal of making available new methods for the treatment of diseases and for the rational modification of biological function.
Studies on the stereoselective synthesis of C-allyl glycosides. McGarvey GJ, LeClair CA, Schmidtmann BA. Org Lett. 10, 4727-30 (2008).
The preparation of C-glycosyl amino acids – an examination of olefin cross-metathesis. Schmidtmann FW, Benedum TE, McGarvey GJ. Tetrahedron letters. 46, 4677-4681 (2005).
Synthesis of alpha- and beta-C-glycosides of N-acetylglucosamine. McGarvey GJ, Schmidtmann FW, Benedum TE, Keizer DE. Tetrahedron letters. 44, 3775-3779 (2003).
Development of co- and post-translational synthetic strategies to C-neoglycopeptides. McGarvey GJ, Benedum TE, Schmidtmann FW. Org Lett. 4, 3591-4 (2002).