Abstract

This research will develop enzymatic methods and combined chemical? and enzymatic methods for the synthesis of bioactive molecules. It will focus? on the following programs: 1) Develop enzymatic asymmetric aldol reactions,? especially for the synthesis of novel iminocyclitols for design of new enzyme? inhibitors; 2) Develop new methods for synthesis of glycopeptides,? glycoproteins, and sulfated glycopeptides. 3) Develop new chemicoenzymatic? synthesis of the anti-cancer agents epothiolones and analogs. 4) Apply? enzyme-catalyzed synthesis to tackle the problems in biochemistry and drug? discovery: develop new assays, prepare glycosyltransferases enzyme substrates? and inhibitors and design cell-surface sugar receptors. Significant? contributions in the areas of biomedicine and synthetic organic chemistry are? expected. This research program should facilitate the discovery and development? of new therapeutic agents.?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM044154-18
Application #
7159373
Study Section
Special Emphasis Panel (NSS)
Program Officer
Jones, Warren
Project Start
1998-03-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
18
Fiscal Year
2007
Total Cost
$430,396
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Lewis, Jared C; Bastian, Sabine; Bennett, Clay S et al. (2009) Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases. Proc Natl Acad Sci U S A 106:16550-5
Hanson, Sarah R; Culyba, Elizabeth K; Hsu, Tsui-Ling et al. (2009) The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability. Proc Natl Acad Sci U S A 106:3131-6
Wu, Douglass; Fujio, Masakazu; Wong, Chi-Huey (2008) Glycolipids as immunostimulating agents. Bioorg Med Chem 16:1073-83
Bennett, Clay; Dean, Stephen; Payne, Richard et al. (2008) Sugar-Assisted Glycopeptide Ligation with Complex Oligosaccharides: Scope and Limitations. J Am Chem Soc :
Sugiyama, Masakazu; Hong, Zhangyong; Greenberg, William A et al. (2007) In vivo selection for the directed evolution of L-rhamnulose aldolase from L-rhamnulose-1-phosphate aldolase (RhaD). Bioorg Med Chem 15:5905-11
Yang, Yu-Ying; Ficht, Simon; Brik, Ashraf et al. (2007) Sugar-assisted ligation in glycoprotein synthesis. J Am Chem Soc 129:7690-701
Hanson, Sarah R; Hsu, Tsui-Ling; Weerapana, Eranthie et al. (2007) Tailored glycoproteomics and glycan site mapping using saccharide-selective bioorthogonal probes. J Am Chem Soc 129:7266-7
Polat, Tulay; Wong, Chi-Huey (2007) Anomeric reactivity-based one-pot synthesis of heparin-like oligosaccharides. J Am Chem Soc 129:12795-800
Hanson, Sarah R; Whalen, Lisa J; Wong, Chi-Huey (2006) Synthesis and evaluation of general mechanism-based inhibitors of sulfatases based on (difluoro)methyl phenyl sulfate and cyclic phenyl sulfamate motifs. Bioorg Med Chem 14:8386-95
Chapman, Eli; Bryan, Marian C; Wong, Chi-Huey (2003) Mechanistic studies of beta-arylsulfotransferase IV. Proc Natl Acad Sci U S A 100:910-5

Showing the most recent 10 out of 11 publications