Complex carbohydrate synthesis tools for glycobiologists
Complex Carbohydrates Synthesis tools for glycobiologists: enzyme-based approach and programmable one-pot strategies
Carbohydrates play important structural and functional roles in numerous physiological processes, including various disease states (Varki, 1993; Dwek, 1996; Sears and Wong, 1998). The relatively recent recognition of carbohydrates as a medicinally relevant class of biomolecules has led to the investigation of therapeutic agents based on either glycan structure or mimics thereof (Figure 1; Sears and Wong, 1999). For example, cancer cell metastasis (Hakomori and Zhang, 1997) and cell–cell adhesion in the inflammatory response (Kansas, 1996) are dependent on cell surface presentation of specific glycans. Synthetic carbohydrate-based cancer vaccines (Danishefsky and Allen, 2000) and small molecule selectin inhibitors (Simanek et al., 1998) are therefore being pursued as potential medicinal agents, respectively.
Likewise, the initial stages of bacterial or viral infection often rely on the recognition of host cell glycoconjugates by the invading organism (Karlsson, 1995). Consequently, naturally occurring and designed synthetic antibiotics frequently contain carbohydrate structures for the disruption of these deleterious interactions (Williams and Bardsley, 1999). Additionally, xenotransplant rejection is due to an undesirable anti-α-Gal antibody induced immune response. Various treatment strategies based on synthetic α-Gal derivatives are under study, with the future goal that foreign tissue be an acceptable organ source for human transplants (Chen et al., 1999). These examples illustrate only a few of the biologically relevant processes in which glycoconjugates are involved. As knowledge of their diverse physiological roles increases, research into carbohydrate-based therapeutics will continue to accelerate.
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