Oligosaccharide metabolic engineering: Applications in boron neutron capture cancer therapy

CARB 82

Xing Chen, chenxing@berkeley.edu, Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720 and Carolyn R. Bertozzi, crb@berkeley.edu, Departments of Chemistry and Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720-1460.
Boron neutron capture therapy (BNCT), initially developed in 1950s, has attracted lot of attention in recent years. Selective targeting of BNCT reagents to tumors is one of the key components of this cancer therapy procedure. Tumor cell surfaces exhibit abnormal glycosylation and many tumor-associated carbohydrate antigens possess the monosaccharide sialic acid, and indeed, the overexpression of sialic acid has been correlated with the malignant and metastatic phenotypes. Here we present a strategy for the selective delivery of BNCT reagents to tumor cells that exploits intrinsic differences in sialic acid expression. The approach capitalizes on the unnatural substrate tolerance of the enzymes in the sialoside biosynthetic pathway, which allows the metabolic conversion of boron containing unnatural sialic acid to the corresponding sialosides in human cells. The synthesis of unnatural sialic acids and the initial biological studies will be presented.
 

Chemical Glycobiology Symposium
7:00 PM-9:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Carbohydrate Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006