Abstract

This research will develop enzymatic methods and combined chemical and enzymatic methods for the synthesis of bioactive molecul3es. 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 #
2R37GM044154-12
Application #
6286984
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Jones, Warren
Project Start
1989-09-01
Project End
2005-11-30
Budget Start
2001-01-05
Budget End
2001-11-30
Support Year
12
Fiscal Year
2001
Total Cost
$355,764
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
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 :
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
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
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