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Modular Automation and Chemical Methods for S- and O-linked Plant and Microbial Carbohydrate Synthesis

S-和O-连接植物和微生物碳水化合物合成的模块化自动化和化学方法

基本信息

批准号：
1955936
负责人：
Nicola Pohl
金额：
$ 45万
依托单位：
Indiana University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-15 至 2024-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1955936&HistoricalAwards=false
关键词：
Modular Automation Chemical Methods linked

项目摘要

With this award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Nicola Pohl of the Department of Chemistry at Indiana University in Bloomington. Professor Pohl is developing automated tools to construct carbohydrates bearing S-linkages a feature that stabilizes the carbohydrate polymers in biological systems. Carbohydrate chains known as oligosaccharides are found in every organism—from plants to humans to microbes—as well as on the surfaces of viruses. These organisms also contain glycosidases, biological catalysts that can cleave carbohydrate linkages. More stable oligosaccharides are needed to study the biological activity of linked sugars and to design glycosidase inhibitors. Professor Pohl and her students are developing new automated tools to create oligosaccharides associated with plants and microbes that include specific features that will allow them to be used to study proteins that assemble and dismantle these chains. This research is impacting plant studies, as well as providing foundational understanding for the agricultural and pharmaceutical industries. In addition to training the students in her research group in the development and use of information technology (IT)-enabled automation, Professor Pohl is also building a new undergraduate laboratory curriculum that aims to expose undergraduate students to synthetic automation and carbohydrate synthesis. There is a critical need for the development of automated methods for the synthesis of defined oligosaccharides to support studies on the activities of these compounds in biological systems. Professor Pohl and her research team are developing the first glycosylation reactions for S-linked sugars that are amenable to automated liquid-handling. The Pohl group is pursuing the automated synthesis of S-linked sugars due to their greater metabolic stability, a key feature that facilitates their study in biological systems. Automated synthetic methods for S-linked sugars are being developed under batch and continuous flow conditions. Simultaneously, Professor Pohl and her students are developing low-cost flexible automated systems to allow the efficient site-selective incorporation of both O- and S-linkages into plant and microbial oligosaccharides in multi-step syntheses. These research activities are training students at the undergraduate and graduate levels to work at the interface of synthetic organic chemistry and information technology (IT)-enabled automation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过这一奖项，化学系的化学合成计划正在支持位于布鲁明顿的印第安纳大学化学系尼古拉·波尔教授的研究。波尔教授正在开发自动化工具来构建含有S连接的碳水化合物，这是一种稳定生物系统中碳水化合物聚合物的特征。碳水化合物链被称为低聚糖，存在于所有有机体中--从植物到人类再到微生物--以及病毒表面。这些生物体还含有糖苷酶，这是一种可以裂解碳水化合物连接的生物催化剂。为了研究连接糖的生物活性和设计糖苷酶抑制剂，需要更稳定的寡糖。波尔教授和她的学生正在开发新的自动化工具，以创造与植物和微生物相关的低聚糖，这些低聚糖包含特定的功能，可以用来研究组装和拆卸这些链的蛋白质。这项研究正在影响植物研究，并为农业和制药行业提供基础性的理解。除了培训她研究小组中的学生开发和使用信息技术(IT)自动化之外，Pohl教授还在建立一个新的本科实验室课程，旨在让本科生接触合成自动化和碳水化合物合成。迫切需要开发合成确定的寡糖的自动化方法，以支持对这些化合物在生物系统中的活性的研究。波尔教授和她的研究团队正在为S连接的糖开发第一个糖基化反应，这种反应可以自动进行液体处理。POHL团队正在致力于S连接糖的自动化合成，因为它们具有更高的代谢稳定性，这是促进他们在生物系统中研究的一个关键特征。在间歇和连续流动条件下，正在开发S连接糖的自动化合成方法。同时，Pohl教授和她的学生正在开发低成本、灵活的自动化系统，以便在多步合成中高效地将O-和S-键结合到植物和微生物低聚糖中。这些研究活动正在培训本科生和研究生在合成有机化学和信息技术(IT)自动化的界面上工作。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。