CAREER: A Systematic Investigation of Protein-Septanose Interactions

University Of Connecticut, Storrs CT

Investigators

Abstract

With the support of the Organic and Macromolecular Chemistry Program, Professor Mark Peczuh, of the Department of Chemistry at the University of Connecticut, will study the interactions between lectins and unnatural seven membered ring sugars (septanoses). Integral to the approach will be the development of structure activity relationships among a number of septanose-containing carbohydrates based on their relative affinities to the target proteins. A combination of organic synthesis, conformational analysis, and binding studies will be used to determine how septanoses are recognized. Interactions will be evaluated by conducting isothermal titration calorimetry (ITC) and NMR Saturation Transfer Difference (STD) experiments using the synthesized septanose sugars and Concanavalin A (ConA) and Maltose Binding Protein (MBP). The results of these investigations will elucidate how proteins recognize the unnatural sugars and provide a starting point for the development of septanose-based inhibitors of protein function. The Organic and Macromolecular Chemistry program is supporting Professor Mark Peczuh of the Department of Chemistry at the University of Connecticut who will concurrently investigate septanose conformational preferences and protein-septanose binding behavior that will rapidly provide key information for understanding protein-carbohydrate interactions generally and will motivate the design of septanose carbohydrates with potential therapeutic applications. The research will also train students in the theoretical and technical aspects of experimental bioorganic chemistry. Professor Peczuh will also work to dispel common misconceptions about science and scientists among the public by making science more accessible to a broader audience, which should increase interest in the sciences and lead to well reasoned corporate and public policy. Thus, a 'Chemistry in Literature' course taught in conjunction with the English Department will explore the dynamic and creative nature of the scientific process, the generality of analytical thinking, and the idea that discovery is a human process influenced by societal as well as scientific pressures. The course is designed to impact a diverse target audience to maximize its effectiveness.