Document Detail

Chemoenzymatic synthesis and enzymatic analysis of 8-modified cytidine monophosphate-sialic acid and sialyl lactose derivatives.
MedLine Citation:
PMID:  20557044     Owner:  NLM     Status:  MEDLINE    
The sialic acids found on eukaryotic glycans have remarkably diverse core structures, with a range of modifications at C5, C7, C8 and C9. These carbohydrates have been found to play key roles in cell-cell interactions within eukaryotes and often serve as the initial site of attachment for viruses and bacteria. Consequently simple changes to the structures of the sialic acids can result in profoundly different and often opposing biological effects. Of particular importance are modifications at the 8-position. These include O-acetylation, carried out by an acetyl transferase, and particularly polysialylation, catalyzed by a polysialyltransferase. As part of a structural and mechanistic study of sialyltransferases and polysialyltransferases, access was needed to sialic acid-containing oligosaccharides that are modified at the 8-position of the sialic acid to render this center non-nucleophilic. The free 8-modified sialic acid analogues were synthesized using a concise, divergent chemical synthetic approach, and each was converted to its cytidine monophosphate (CMP) sugar donor form using a bacterial CMP-sialic acid synthetase. The transfer of each of the modified donors to lactose by each of two sialyltransferases was investigated, and kinetic parameters were determined. These yielded insights into the roles of interactions occurring at that position during enzymatic sialyl transfer. A transferase from Campylobacter jejuni was identified as the most suitable for the enzymatic coupling and utilized to synthesize the 8''-modified sialyl lactose trisaccharides in multimilligram amounts.
Thomas J Morley; Stephen G Withers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  132     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-07     Completed Date:  2010-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9430-7     Citation Subset:  IM    
Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver V6T 1Z1, Canada.
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MeSH Terms
Campylobacter jejuni / enzymology
Cytidine Monophosphate / chemistry*
Lactose / chemical synthesis*,  chemistry
Polysaccharides / chemistry
Sialic Acids / chemical synthesis,  chemistry*
Sialyltransferases / metabolism
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Polysaccharides; 0/Sialic Acids; 63-37-6/Cytidine Monophosphate; 63-42-3/Lactose; EC 2.4.99.-/Sialyltransferases

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