Novel chemical tools to elucidate carbohydrate chemistry

阐明碳水化合物化学的新型化学工具

• 批准号: 405352613
• 负责人: Professor Dr. Kevin Pagel
• 金额: --
• 依托单位: Institut für Chemie und Biochemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405352613?language=en
• 关键词: Novel; chemical; tools; elucidate; carbohydrate

Complex carbohydrates are among the most versatile biomolecules, playing diverse and essential roles in virtually every living system. Additionally, as key mediators in biological processes, they form the basis for the development of glycomimetic drugs and vaccines.Due to the absence of amplification techniques and expression systems, chemical synthesis offers the most efficient way to access glycans in pure form. The complex and time consuming syntheses have been significantly accelerated by the development of automated glycan assembly by WG Seeberger, providing straightforward access to a wide variety of glycans. However, the detailed mechanism of the glycosidic bond formation – the elementary reaction in glycan synthesis – remains poorly understood. Two limitations exist in the study of these mechanistically rich and structurally complex linkage reactions: the controlled, reproducible optimization of each new coupling, and rapid, data-rich analytics.The joint project of WG Seeberger and WG Pagel aims at the better understanding of the underlying mechanisms of glycosidic bond formation. WG Seeberger will utilize the controlled microreactor synthesis platform to optimize experimental parameters and conditions. The resulting changes in identity and proportion of intermediates, products and byproducts will afterwards be probed by ion mobility-mass spectrometry in WG Pagel. The systematic analysis of the resulting comprehensive dataset will expand the knowledge about glycan intermediates and form the basis for their development of predictive models for glycosylation reactions.

复杂碳水化合物是用途最广泛的生物分子之一，几乎在每个生命系统中都发挥着多样化且重要的作用。此外，作为生物过程中的关键介质，它们构成了糖模拟药物和疫苗开发的基础。由于缺乏扩增技术和表达系统，化学合成提供了获得纯形式聚糖的最有效方法。 WG Seeberger 开发的自动化聚糖组装技术显着加速了复杂且耗时的合成，提供了直接获取各种聚糖的方法。然而，糖苷键形成的详细机制（聚糖合成中的基本反应）仍然知之甚少。这些机制丰富且结构复杂的连接反应的研究存在两个局限性：每个新偶联的受控、可重复的优化，以及快速、数据丰富的分析。 WG Seeberger 和 WG Pagel 的联合项目旨在更好地理解糖苷键形成的潜在机制。 WG Seeberger 将利用受控微反应器合成平台来优化实验参数和条件。随后将通过 WG Pagel 中的离子淌度-质谱法来探测由此产生的中间体、产物和副产物的特性和比例的变化。对所得综合数据集的系统分析将扩展有关聚糖中间体的知识，并为开发糖基化反应预测模型奠定基础。