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

NIH RePORTER · NIH · R21 · $205,151 · view on reporter.nih.gov ↗

Abstract

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.

Key facts

NIH application ID
10891709
Project number
5R21GM151612-02
Recipient
IOWA STATE UNIVERSITY
Principal Investigator
Arthur H. Winter
Activity code
R21
Funding institute
NIH
Fiscal year
2024
Award amount
$205,151
Award type
5
Project period
2023-08-01 → 2026-07-31