American Chemical Society - Division of Carbohydrate Chemistry ...

study of bioactive glycopeptides and semisynthetic glycoprotein conjugates.
These studies will be presented with a focus on the effects of N-linked
glycosylation on diabetes related peptides and glycosylated antibody fragments.
N-linked glycosylation has proven to have some unexpected effects on the
physical properties and bioactivity of glycoconjugates in these systems that may
be useful in the development of glycopeptide and glycoprotein therapeutics.
(1) Journal of the American Chemical Society 2010, 132, 3211-3216.
(2) Journal of the American Chemical Society 2009, 131, 13616-13618.
CARB 11
Efficient chemoenzymatic synthesis of sialyl Lewis antigens using
sialyltransferase mutants
Xi Chen (1) , chen@chem.ucdavis.edu, One Shields Avenue, Davis CA 95616,
United States ; Go Sugiarto (1) ; Kam Lau (1) ; Lei Zhang (1) ; Shengshu Huang (1) . (1)
Department of Chemistry, University of Califorina-Davis, Davis California 95616,
United States
Sialic acids are a family of nine-carbon monosaccharides mainly found as the
terminal residues of glycans on cell surfaces (1). More than 50 structurally
distinct sialic acids have been found in nature (2, 3). Sialyl Lewis x is an important
sialic acid-containing carbohydrate epitope involved in many biological processes
such as inflammation (4) and cancer metastasis (5). Sialyl Lewis a is also involved
in cancer progression (6). One of our research goals is to develop efficient
chemoenzymatic method for the synthesis of sialyl Lewis x and sialyl Lewis a
oligosaccharides containing structurally diverse sialic acid residues.
The general biosynthetic pathway of sLe x and sLe a involves sialylation followed
by fucosylation. In order to obtain sLe x and sLe a containing structurally diverse
sialic acids, a more efficient approach would be to carry out the fucosylation
before the sialylation so that different sialic acid forms can be introduced in the
last glycosylation step. However, most sialyltransferases reported can not
tolerate fucosylated substrates except for a viral alpha2,3-sialyltransferase (v-
ST3Gal I) from myxoma virus (7). We have successfully cloned and expressed
the v-ST3Gal I in E. coli. The enzyme has been used in the sialylation of Lewis x
antigen. In addition, mutants of Pasteurella multocida sialyltransferase 1
(PmST1), a multifunctional alpha2,3-sialyltransferase that has excellent
expression level, solubility, and activity towards non-fucosylated substrates, have
been designed and generated for direct sialylation of fucosylated
oligosaccharides.
1. Varki, A. (1997) Sialic acids as ligands in recognition phenomena, FASEB J.
11, 248–255.
2. Angata, T., and Varki, A. (2002) Chemical diversity in the sialic acids and