| Chemoenzymatic synthesis and enzymatic analysis of 8-modified cytidine monophosphate-sialic acid and sialyl lactose derivatives. | |
| | |
MedLine Citation:
|
PMID: 20557044 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Thomas J Morley; Stephen G Withers |
Related Documents
:
|
15051544 - An integrity assay for a meningococcal type b conjugate vaccine. 8918804 - Molecular cloning of the cdna encoding a murine sialic acid-specific 9-o-acetylesterase... 6530404 - Ganglioside pattern of normal human brain, from samples obtained at surgery. a study es... 15280024 - Biochemical engineering of the n-acyl side chain of sialic acid leads to increased calc... 9492384 - Biotransformation of 13-cis- and 9-cis-retinoic acid to all-trans-retinoic acid in rat ... 2051164 - Anomalously high concentrations of brain extracellular uric acid detected with chronica... |
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 |
Affiliation:
|
Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver V6T 1Z1, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Campylobacter jejuni
/
enzymology Cytidine Monophosphate / chemistry* Lactose / chemical synthesis*, chemistry Polysaccharides / chemistry Sialic Acids / chemical synthesis, chemistry* Sialyltransferases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
|
0/Polysaccharides; 0/Sialic Acids; 63-37-6/Cytidine Monophosphate; 63-42-3/Lactose; EC 2.4.99.-/Sialyltransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Protein Structure-Sensitive Electrocatalysis at Dithiothreitol-Modified Electrodes.
Next Document: E-Type Delayed Fluorescence of a Phosphine-Supported Cu(2)(mu-NAr(2))(2) Diamond Core: Harvesting Si...