The Pohl research group is finding new ways to make and analyze sugars to dissect their important roles in plant, animal, and human biology and to design therapeutics. We do this through the development of human-friendly automation and readily reproducible chemistry.

One major long-term goal is to rationally design therapeutic interventions such as vaccines and glycoproteins based on a deeper knowledge of the role of carbohydrates. Unfortunately, tools to study glycans are lacking when compared to those available to study proteins and nucleic acids. Figuring out the exact differences in surface carbohydrates between a pathogenic and nonpathogenic strain of bacteria, for example, is a daunting and time-consuming process; making an exact replica of the structure in the lab can take even longer. Currently, the development of robust analytical techniques for de novo sequencing of glycans is significantly hampered by the lack of authentic standards for comparison. Synthetic efforts are challenged by the scale at which compounds must be made for analysis of their structure rather than of their properties in biological assays.

Our lab is taking a systems approach to solving these intertwined problems of carbohydrate synthesis and analysis. We have redefined the problem of automated oligosaccharide synthesis from the traditional one of “How do we adapt solid-phase peptide synthesizers to make glycans?” to “How do we create automated pathways to make any glycan on demand?”. To this end, we have created the first automated solution-phase method based on fluorous tags to readily synthesize oligosaccharides and more more recently published work on the automated synthesis of building blocks needed to feed our (and others) automated oligosaccharide synthesis machines. These automated methods and the concept of Glycans On Demand circumvent key problems encountered with the solid-phase approaches that allowed commercial automated synthesis of other biopolymers like DNA and peptides.

In parallel, we have created the first methods to use mass spectrometry—a technique that uses very low sample volumes—to identify a range of carbohydrates that share molecular weights as a first step in designing a full process for de novo carbohydrate sequencing. We are especially grateful to the US National Science Foundation, the US National Institutes of Health, the Joan and Marvin Carmack Fund, the excellent staff and facilities at Indiana University for currently enabling this science, and our collaborators at IU, MIT, U. Iowa, Virginia Tech, Mayo, Harvard Med, U. Delaware, Tufts, CalTech, U. Wisc. and Wayne State!

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