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

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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.