Development of Methods for the Automated Synthesis of Plant and Microbial Oligosaccharides

通过这个奖项，由化学系的化学合成计划资助，来自印第安纳州布卢明顿大学的Nicola Pohl教授和她的学生解决了研究一类重要的生物分子聚糖的两个障碍，聚糖是含有糖链的生物活性分子。 这些障碍包括缺乏简单的化学方法来制造定义明确的糖片段，以及缺乏教育材料来向早期的化学家和生物学家介绍这类生物分子。这项拟议研究的更广泛影响包括：1）通过将代表性不足的群体纳入拟议的研究和教育活动，增加他们的参与; 2）通过将研究生和本科生纳入参与者，促进发现和理解; 3）开发和传播概述碳水化合物在新陈代谢之外的作用的教育材料;以及4）开发用于合成植物、病毒和微生物寡糖的稳健的自动化方法，这是该研究领域进展的瓶颈，因为大量的这些材料对于研究它们在各种生物材料中的功能是必需的，该项目涉及研究和开发铋（V）络合物的机制，该络合物被发现用于促进使用烷基硫醇连接的糖的糖基化反应。这项研究的目的是更好地了解这种相对无毒的元素可以影响的化学反应，并在此过程中获得如何加速糖基化反应的线索。此外，将探索将这种新的启动子应用于自动化溶液相寡糖合成的协议，并开发用于生产与重要植物和微生物生物活性相关的较大生物活性结构的可行构建块策略。

Through this award, funded by the Chemical Synthesis Program of the Division of Chemistry, Prof. Nicola Pohl from Indiana University-Bloomington and her students address two impediments to study of an important class of biomolecules called glycans, which are bioactive molecules containing linked chains of sugars. These stumbling blocks include both the lack of facile chemical methods to make well-defined sugar fragments and the availability of educational materials for introducing this class of biomolecules to budding chemists and biologists very early in their advanced education. The broader impacts of this proposed research include: 1) increasing participation of underrepresented groups by their inclusion in the proposed research and education activities; 2) advancing discovery and understanding through inclusion of graduate and undergraduate students as participants; 3) developing and disseminating educational materials that outline the role of carbohydrates beyond metabolism; and 4) developing robust automated methods to synthesize plant, viral and microbial oligosaccharides, a bottleneck to advancement of this line of research, since significant quantities of these materials are necessary for the study of their functions in a variety of biological, materials, and medical contexts.This project involves study and exploitation of the mechanism of a bismuth(V) complex discovered to promote glycosylation reactions using alkylthiol-linked sugars. The goal of the study is to better understand the chemistry that this relatively nontoxic element can effect and, in the process, to gain clues for how the glycosylation reaction can be accelerated. In addition, protocols to apply this new promoter to automated solution-phase oligosaccharide synthesis and to develop feasible building block strategies for the production of larger bioactive structures associated with important plant and microbial saccharides will be explored.