4. Carbohydrate Microarrays

While the importance of carbohydrates in biological systems is well documented, screening techniques to further elucidate their function are still needed. Solid-phase attachment on a microtiter plate would therefore provide an ideal basis for the facile and high-throughput analysis of structure-function relationships of carbohydrates with various biological functionalities (nucleic acids, proteins, etc). Our lab is currently trying to develop oligosaccharide and aminoglycoside arrays, and new methods have been developed for covalent and noncovalent interactions between sugars and polystyrene or glass surfaces for highthroughput analysis. Using these arrays, we hope to screen complex carbohydrate libraries to identify ligands and define specificity of carbohydrate-protein interactions. We also have applied this display strategy to further modifying carbohydrates in situ via enzymatic reactions to further increase library diversity.

Figure 4A. Attachment of carbohydrates to microtiter plate surfaces 1 glass slide or glass slides coated with aluminum oxide. Carbohydrates can then be screened against a variety of biologically important substrates such as lectins, antibodies and RNA. (J. Am. Chem. Soc. (2002) 124, 14397); (2010), 132, 14849–56; (2010), 132, 13371–80; PNAS (2009) 106, 18137–42.

Figure 4B. Differentiation and detection of influenza hemagglutinin subtypes using glycan microarrays. (JACS (2010) 132, 14849–56).

Figure 4C. in situ attachment of sugars to microtiter plates via 1,3-dipolar cycloaddition between alkynes and azides. Carbohydrates displaying terminal azides can be captured on microtiter plate surfaces through a terminal alkyne attached to a long, aliphatic tether and screened directly on the microtiter plate surface. (J. Am. Chem. Soc. (2002) 124, 14397; J. Am. Chem. Soc. (2004) 126, 8640)

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