Probing the substrate specificity of human golgi alfa-mannosidase II using synthetic oligosaccharides

CARB 37

Wei Zhong, wzhong@chem.uga.edu, Brian Ember, and Geert-Jan Boons, gjboons@ccrc.uga.edu. Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602
Inhibition of the mannose trimming enzyme human Golgi alfa-mannosidase II (HGMII), which acts late in the N-glycan processing pathway, provides one route to blocking the oncogene-induced changes in cell surface oligosaccharide structures. HGMII selectively cleaves alfa 1-3 and alfa 1-6 mannosyl residues present in its natural substrate GlcNAcMan5GlcNAc2. It has been proposed that HGMII has an extended binding site recognizing a large part of the oligosaccharide. In order to probe the substrate requirements of HGMII, we have synthesized a range of part-structures of GlcNAcMan5GlcNAc2 and determined kinetic parameters for hydrolysis by HGMII. The resulting information has been employed for the design of inhibitors for this enzyme.
 

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The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006