This project addresses the development of a novel chemo-enzymatic method for the synthesis of complex carbohydrates. This unconventional method is especially useful in obtaining structurally defined complex oligosaccharides and polysaccharides. Enzymes active in the formation of glycosidic linkages from monosaccharide substrates will be recruited to act upon disaccharide substrates. This chemistry will be exploited for the synthesis of oligosaccharides and polysaccharides containing non-terminal sialic acid residues and structurally defined heparin/heparan sulfate. Enzyme-catalyzed reactions (e.g. aldolase-catalyzed reactions) will be exploited on the educational front as well, introducing coordinated lecture and laboratory content to the undergraduate curricula (for both chemistry and biology majors, including premedical students). Comparisons with similar non-enzymatic organic reactions will serve as a springboard for additional discussions. Through the ACS Project SEED program, economically disadvantaged high school students will be introduced to the broad picture of interdisciplinary research.
With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Xi Chen, of the Department of Chemistry at the University of California at Davis, is exploring new methods for the synthesis of complex polysaccharides (sugars). Professor Chen is developing a novel chemo-enzymatic synthetic method to obtain these structures, which are difficult to obtain through conventional chemical and enzymatic synthesis. By taking advantage of the flexibility of some enzymes with regards to the molecules upon which they act, Professor Chen is able to recruit these enzymes to produce more complex products than those they were designed by Nature to produce. Access to these complex products is essential for development of our understanding of the numerous biological and biochemical processes in which polysaccharides play key roles, including cellular recognition and adhesion phenomena. Consideration of the methods by which enzymes catalyze organic reactions will also be brought to the undergraduate lecture and laboratory programs, with comparisons with non-enzymatic processes providing an interesting platform for student discussion and learning. Economically disadvantaged high school students will be introduced to the broad picture of interdisciplinary research through the ACS Project SEED program.
