Photochemical Technologies for Improved Glycosylation Reactions

用于改进糖基化反应的光化学技术

• 批准号: 10627108
• 负责人: David Crich
• 金额: $ 21.74万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10627108
• 关键词: Address; Alcohols; Anions; Biological; Biological Process; Biology; Carbohydrates; Cations; Chemistry; Communities; Development; Disease; Esters; Fluorides; Glycoconjugates; Glycols; Glycosides; Goals; Health; Human; Ions; Light; Medicine; Methodology; Methods; Oligonucleotides; Oligosaccharides; Peptides; Play; Polysaccharides; Preparation; Protocols documentation; Reaction; Reagent; Regulation; Reproducibility; Role; Source; Specialist; System; Technology; Testing; catalyst; chemical synthesis; design; glycosylation; improved; innovation; irradiation; light emission; new technology; novel; nucleophilic substitution; operation; promoter; scale up

Carbohydrates, glycans, and their conjugates play critical roles in a very broad spectrum of biological processes, many of which are central to human health, development and disease states. The diversity of glycan-dependent biological processes is reflected by the even-more diverse spectrum and complexity of the implicated glycans and glycoconjugates, collectively known as the glycome. The study of glycan dependent biological processes and their eventual regulation and/or exploitation in human medicine is enormously hampered by difficulties in isolating and structurally characterizing meaningful quantities of pure unique glycans, known as homogeneous glycoforms, from biological sources. It is imperative therefore that simple practical technologies for glycan synthesis be developed that combine robustness with ease of operation such that specialist and non-specialists alike will be able to access glycans with relative ease. This proposal aims to develop exactly the kind of scalable robust methodology that is required to address the chemical synthesis of a broad cross section of the glycome. The focus is on the development of direct photochemical methods without the need for external additives thereby reducing the system to its essentials – a glycosyl donor and glycosyl acceptor – and eliminating complexity to the greatest extent possible. The technologies to be developed are designed to employ light-emitting diodes (LEDs) as light sources and ultimately to be applicable under flow conditions so as to enable practical scaled-up syntheses of biologically important glycans.

碳水化合物，聚糖及其缀合物在非常广泛的 生物过程的范围，其中许多是人类健康的核心， 发展和疾病状态。聚糖依赖性生物学的多样性 流程由偶数潜水的频谱和复杂性反映 暗示的聚糖和糖缀合物，统称为糖斑点。研究 依赖聚糖的生物过程及其最终调节和/或 人类医学中的剥削受到隔离和孤立和 结构表征有意义的纯独特聚糖，称为 来自生物学来源的均质糖型。因此，必须简单 可以开发用于聚糖合成的实用技术，将鲁棒性与 易于操作，使专家和非专家都可以访问 相对轻松的聚糖。该建议旨在完全发展那种可扩展的 解决宽十字的化学合成所需的强大方法论 Glyce的部分。重点是直接光化学的发展 方法无需外部添加剂，从而将系统减少到其 必需品 - 糖基供体和糖基受体 - 并消除对 最大程度的可能性。要开发的技术旨在采用 发光语音（LED）作为光源，最终适用于流量 条件以实现生物学上重要的实际扩增合成 聚糖。