Document Detail

Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor treatment.
MedLine Citation:
PMID:  17172262     Owner:  NLM     Status:  MEDLINE    
The inherent promiscuity of the polysialic acid (PSA) biosynthetic pathway has been exploited by the use of exogenous unnatural sialic acid precursor molecules to introduce unnatural modifications into cellular PSA, and has found applications in nervous system development and tumor vaccine studies. The sialic acid precursor molecules N-propionyl- and N-butanoyl-mannosamine (ManPr, ManBu) have been variably reported to affect PSA biosynthesis ranging from complete inhibition to de novo production of modified PSA, thus illustrating the need for further investigation into their effects. In this study, we have used a monoclonal antibody (mAb) 13D9, specific to both N-propionyl-PSA and N-butanoyl-PSA (NPrPSA and NBuPSA), together with flow cytometry, to study precursor-treated tumor cells and NT2 neurons at different stages of their maturation. We report that both ManPr and ManBu sialic acid precursors are metabolized and the resultant unnatural sialic acids are incorporated into de novo surface sialylglycoconjugates in murine and human tumor cells and, for the first time, in human NT2 neurons. Furthermore, neither precursor treatment deleteriously affected endogenous PSA expression; however, with NT2 cells, PSA levels were naturally downregulated as a function of their maturation into polarized neurons independent of sialic acid precursor treatment.
Robert A Pon; Nancy J Biggs; Harold J Jennings
Publication Detail:
Type:  Journal Article     Date:  2006-12-15
Journal Detail:
Title:  Glycobiology     Volume:  17     ISSN:  0959-6658     ISO Abbreviation:  Glycobiology     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-19     Completed Date:  2007-05-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  249-60     Citation Subset:  IM    
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Canada.
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MeSH Terms
Antibodies, Monoclonal / immunology
Biomedical Engineering / methods
Cell Line, Tumor
Cell Membrane / chemistry
Flow Cytometry
Hexosamines / metabolism,  pharmacology
N-Acetylneuraminic Acid / biosynthesis
Neurons / drug effects,  metabolism*,  ultrastructure
Polysaccharides / analysis,  biosynthesis*,  immunology
Polysaccharides, Bacterial / analysis,  biosynthesis*,  immunology
Sialic Acids / biosynthesis*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Hexosamines; 0/N-butanoylmannosamine; 0/N-butanoylpolysialic acid; 0/N-propionylmannosamine; 0/N-propyl group B meningococcal polysaccharide; 0/Polysaccharides; 0/Polysaccharides, Bacterial; 0/Sialic Acids; 0/polysialic acid; 131-48-6/N-Acetylneuraminic Acid

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