Chromatically Orthogonal Photolabile Protecting Groups for the Parallel On-Chip Synthesis of High-Density Glycan Microarrays

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Abstract. The objective of this research is to identify carbohydrate-compatible photolabile protecting groups and light sources to facilitate the parallel on-surface synthesis of high-density glycan microarrays—e.g. glycan chips—in a manner similar to the synthesis of gene chips. Instead of using monochromatic light and a single photolabile protecting group to spatially control the extension of a linear polymer (DNA) on the microchip, as in gene chip manufacture, irradiation with different wavelengths of light combined with wavelength-selective tem- porary protecting groups will allow for constructing complex, branched glycans on a microchip surface. I aim to: (1) identify carbohydrate-compatible photolabile protecting groups and optimal light sources to pair with each; and (2) identify a pair of wavelength-selective (`chromatically orthogonal') protecting groups and demonstrate their use in branched glycan synthesis, paving the way towards the parallel on-chip synthesis of high-density glycan microarrays. Wavelength-selective photochemistry will be achieved by separating the absorptions of pho- tolabile protecting groups to allow for selective excitation. Such high-density combinatorially-synthesized glycan chips are expected to permit rapid epitope mapping and screening of the selectivity of glycan binding partners. For example, exposing a dye-labeled lectin, antibody, or virus/bacteria/pathogen binding protein to the chip will allow its binding specificity for numerous glycan structures to be determined from a single experiment. The ability to synthesize high-density combinatorial libraries of carbohydrates will aid in resolving the structure-function relationships of carbohydrates, help to understand the target epitopes of glycan binding partners, and accelerate efforts to uncover the structure and function of the glycome.