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1. Natural and Synthetic Glycolipids and Glycoconjugates as Medicines 1. Glycosyltransferases and glycomics Chemical Biology of Carbohydrates: 1.Basic.

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Presentation on theme: "1. Natural and Synthetic Glycolipids and Glycoconjugates as Medicines 1. Glycosyltransferases and glycomics Chemical Biology of Carbohydrates: 1.Basic."— Presentation transcript:

1 1. Natural and Synthetic Glycolipids and Glycoconjugates as Medicines 1. Glycosyltransferases and glycomics Chemical Biology of Carbohydrates: 1.Basic research on carbohydrate processing enzymes and glycomics 2.Basic research on biosynthesis and biogenesis of complex carbohydrates Glycomedicine: 1.Natural and synthetic glycolipids and glycoconjugates as medicines 2.Glycoproteins as vaccines and medicines Synthetic Biology: 1. Green chemistry and approach to produce pharmaceuticals and chemicals 2. Biosynthetic engineering to produce sugar-protein conjugates Research Programs of Glycoscience in the Wang Lab Our Lab has a longstanding expertise in chemical and/or enzymatic synthesis of natural glycolipids and natural product glycoconjugates which have remarkable biological significance. The following are selected representatives of products which have been accomplished in recent years. 2. Biosynthesis and Biogenesis of Lipopolysaccharide (LPS) Bacterial cell surface polysaccharides, such as lipopolysaccharides (LPSs) play important roles in processes critical to bacterial pathogenicity and immunology. The Wang group has set up a platform to biosynthesize bacterial lipopolysaccharide using purified key proteins Wzy and Wzz in vitro. Through this approach, the biochemical property of those important enzymes will be studied (P.G Wang, et al. Nat. Chem. Biol. 2010, 6, 418–423). The structure of Lipopolysacchride (LPS) Wzy-dependent O-antigen synthesis in E. coli Expression and activity assay of membrane protein Wzy and WzzComparison of Wzy activity among repeating unit donors with variable lipid moieties. Wzy expression LipidGeometryStructurePercent (%) Undecaprenol 7 cis, 3 trans 51 ± 5 Heptaprenol 4 cis, 2 trans 34 ± 4 Pentaprenol 2 cis, 2 trans 15 ± 2 Cis-Pentaprenol 4 cis, 0 trans 29 ± 4 Solanesol 0 cis, 8 trans 0 MS-Pentaprenol 1 cis, 2 trans 3 ± 1 2. Biosynthetic engineering to produce sugar-protein conjugates E. coli O157-CRM197 glyco-conjugate vaccineS. penumoniae 23F-CRM197 glyco-conjugate vaccine 2. Glycoproteins as vaccines and medicines General glycosyltransferase (GT) catalyzed reaction: GT transfers sugar from nucleotide diphoshate (NDP) sugar to an acceptor  Glycomics: comprehensive study of structures and functions of carbohydrates  Elucidate biosynthetic pathways  Biosynthesis of complex carbohydrates Applications of glycosyltransferases:  Donor substrate DHAP is expensive and unstable.  Phosphate group should be removed to obtain the desired product. Flask to E.coli E.Coli Machinery 1.Green chemistry and approach to produce pharmaceuticals and chemicals 1.Funding Support: Research and Development of a Novel System to Produce Polysaccharide Vaccines (NIH R01) Biosynthesis of Polysaccharides (NIH R01 GM085267) Investigation on Oligosaccharides as Antimicrobial and Prebiotics (NIH R01 HD061935) 2.Wang Lab Members: PI: Dr. Peng George Wang Research Scientists: Dr. Lirong Chen, Dr. Jing Song, Dr. Baolin Wu; Postdocs: Dr. Tiehai Li, Dr. Guilong Zhao, Dr. Guohui Zhao; Graduate students: Jarin Joyner, Xu Li, Xifang Liu, Elena Nikonova, Xuan Wang, Mohui Wei, Adriel Williams, Zhongying Xiao, Baoyuan Zhang, Qing Zhang 3.Contact Information Website: http://chemistry.gsu.edu/P_Wang.php Contact information: P. G. Wang (pwang11@gsu.edu)


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