The Striegler Lab



Lab members


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Dept. of Chem. & Biochem.
University of Arkansas
Visitor Information

Dr. Susanne Striegler
Dept. Chem. & Biochem.
210 Chemistry Building
University of Arkansas
Fayetteville, AR 72701
Phone: +1 (479) 575 5079
FAX: +1 (479) 575 4049

We use synthesis, catalysis, biochemistry, and molecular recognition in combination with material science and computation in an interdisciplinary approach to design new potent glycosidase inhibitors, evaluate glycosidase mechanisms and function, and provide new chemical tools for the study of biological events.

Project 1: Designing potent glycosidase inhibitors as new drugs

 Inhibitors of carbohydrate processing enzymes serve as important tools toward an understanding of the mechanisms of the targeted glycosidases. The glyconoamidine family of inhibitors was previously identified as a compound class that contains several putative transition state analogs of glycoside hydrolases. The sp2-hybridized anomeric C-atom of the amidines and their protonation under physiological conditions allow mimicking oxocarbenium ion-like properties of the transition state of glycoside hydrolases. Stabilizing interactions of both the glycon and aglycon of the designed compounds were shown to play a pivotal role in the inhibition of beta-glycosidases. We currently extended our study to include similar compounds for the inhibition alpha-galactosidases and base our efforts on a combination of organic synthesis and computational analysis.

Project 2: Glycosidase mechanisms, structure and function

 The prevalence of glycoside hydrolases in progression and pathology of multiple diseases marks these enzymes as frequent targets during drug development. Glycosides are crucial in many cell-to-cell recognitions including bacterial and viral infections, fertilization,and disease recognition. The complex interactions of glycosides with protein receptors or hydrolases are important for the understanding of underlying recognition processes. Along these lines, we examined galactonoamidines as transition state analogs of beta-galactosidases to elucidate important binding interactions in the active sites, enzyme conformations that support inhibitor binding and the role of proton donors and nucleophiles. In this project we use biochemical methods for protein expression and purification, spectroscopic evaluation of enzyme function and structure that are supported by molecular docking and modeling studies.

Project 3: New catalytic material for carbohydrate transformation

   The catalytic transformation of carbohydrates and their derivates with man-made tools is an alternate approach to the use of enzymes to access glycoconjugates and oligosaccharides of interest. Applying principles learned from Nature, we currently develop macrolecular catalysts with enzyme-like activity that may find use as new antibacterial material to overcome the increasing bacterial resistance against antibiotics. New recipes for synthesis of microgel catalysts at ambient temperature were recently developed and explored showing hydrolytic activity of the macromolecular catalysts toward saccharides that are up to 300,000-fold accelerated over background and 38 times faster than the hydrolysis by corresponding low molecular weight analogs. In this project, we polymerize miniemulsions yielding microgels that are then optimized for catalytic activity in water.