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

用于并行片上合成高密度聚糖微阵列的色谱正交光不稳定保护基团

• 批准号: 10722250
• 负责人: Arthur H. Winter
• 金额: $ 14.86万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10722250
• 关键词: Acceleration; Antibodies; BODIPY; Bacteria; Benign; Binding; Binding Proteins; Biological Process; Carbohydrates; Collaborations; Color; Combinatorial Synthesis; Complex; DNA; DNA Sequence; Darkness; Development; Dyes; Epitope Mapping; Epitopes; Family; Fluorescence; Gene Chips; Genotype; Health; Human; Immune; In Situ; Individual; Label; Lectin; Libraries; Light; Matched Group; Methods; Monitor; Monosaccharides; Neoplasm Metastasis; Oligonucleotides; Outcomes Research; Photochemistry; Polymers; Polysaccharides; Reagent; Research; S phase; Signal Transduction; Source; Specificity; Structure; Structure-Activity Relationship; Surface; Technology; Viral; Virus; Work; absorption; chromophore; combinatorial; density; experience; experimental study; fabrication; gene synthesis; glycosylation; irradiation; manufacture; microchip; pathogen; screening; sugar; trafficking

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.

抽象的。这项研究的目的是确定碳水化合物相容的耐光保护基团 和光源，以促进高密度多糖微阵列的表面平行合成--例如，多糖 芯片--以一种类似于基因芯片合成的方式。代替使用单色光和单色光 耐光性保护基团，用于空间控制微芯片上线性聚合物(DNA)的延伸，如 基因芯片制作，不同波长的光照射结合波长选择的电子显微镜 暂时性保护基团将允许在微芯片表面构建复杂的分枝多聚糖。我的目标是： (1)确定碳水化合物相容的耐光保护基团和与每个基团配对的最佳光源； 和(2)确定一对波长选择性(色正交)保护基并展示 它们在支链多糖合成中的应用，为高密度的并行芯片合成铺平了道路 多聚糖微阵列。波长选择性的光化学将通过分离磷的吸收来实现。 耐受保护基团，以允许选择性激发。这种高密度的组合合成的多糖 芯片有望实现快速表位映射和筛选葡聚糖结合伙伴的选择性。 例如，将染料标记的凝集素、抗体或病毒/细菌/病原体结合蛋白暴露于芯片将 使其对多种糖链结构的结合专一性通过一次实验即可确定。一种能力 合成高密度碳水化合物组合文库有助于结构功能的解析 碳水化合物的相互关系，有助于了解糖链结合伙伴的目标表位，并加速 努力揭开糖糖的结构和功能。