Glycobiology, 2000, Vol. 10, No. 1 11-20
© 2000 Oxford University Press
Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate: inhibition of myelin-associated glycoprotein binding to neural cells
Departments of Pharmacology and 4Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Sialic acids are prominent termini of mammalian glycoconjugates and are key binding determinants for cell–cell recognition lectins. Binding of the sialic acid–dependent lectin, myelin-associated glycoprotein (MAG), to nerve cells is implicated in the inhibition of nerve regeneration after injury. Therefore, blocking MAG binding to nerve cell sialoglycoconjugates might enhance nerve regeneration. Previously, we reported that certain sialoglycoconjugates bearing N-acetylneuraminic acid (NeuAc) but not N-glycolylneuraminic acid (NeuGc) support MAG binding (Collins et al., 1997a). We now report highly efficient conversion of sialic acids on living neural cells from exclusively NeuAc to predominantly NeuGc using a novel synthetic metabolic precursor, N-glycolylmannosamine pentaacetate (ManNGcPA). When NG108–15 neuroblastoma-glioma hybrid cells, which normally express only NeuAc (and bind to MAG), were cultured in the presence of 1 mM ManNGcPA, they expressed 80–90% of their sialic acid precursor pool as NeuGc within 24 h. Within 5 days, 80% of their ganglioside-associated sialic acids and 70% of their glycoprotein-associated sialic acids were converted to NeuGc. Consistent with this result, treatment of NG108–15 cells with ManNGcPA resulted in nearly complete abrogation of MAG binding. These results demonstrate that ManNGcPA treatment efficiently alters the sialic acid structures on living cells, with a commensurate change in recognition by a physiologically important lectin.
1 These two authors contributed equally to this work.
2 Present address: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA
3 To whom correspondence should be addressed at: Department of Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Du, M A. Meledeo, Z. Wang, H. S Khanna, V. D P Paruchuri, and K. J Yarema Metabolic glycoengineering: Sialic acid and beyond Glycobiology, December 1, 2009; 19(12): 1382 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hedlund, P. Tangvoranuntakul, H. Takematsu, J. M. Long, G. D. Housley, Y. Kozutsumi, A. Suzuki, A. Wynshaw-Boris, A. F. Ryan, R. L. Gallo, et al. N-Glycolylneuraminic Acid Deficiency in Mice: Implications for Human Biology and Evolution Mol. Cell. Biol., June 15, 2007; 27(12): 4340 - 4346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Varki and T. Angata Siglecs--the major subfamily of I-type lectins Glycobiology, January 1, 2006; 16(1): 1R - 27R. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Martin, J. C. Rayner, P. Gagneux, J. W. Barnwell, and A. Varki Evolution of human-chimpanzee differences in malaria susceptibility: Relationship to human genetic loss of N-glycolylneuraminic acid PNAS, September 6, 2005; 102(36): 12819 - 12824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bardor, D. H. Nguyen, S. Diaz, and A. Varki Mechanism of Uptake and Incorporation of the Non-human Sialic Acid N-Glycolylneuraminic Acid into Human Cells J. Biol. Chem., February 11, 2005; 280(6): 4228 - 4237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Kim, S.-G. Sampathkumar, M. B. Jones, J. K. Rhee, G. Baskaran, S. Goon, and K. J. Yarema Characterization of the Metabolic Flux and Apoptotic Effects of O-Hydroxyl- and N-Acyl-modified N-Acetylmannosamine Analogs in Jurkat Cells J. Biol. Chem., April 30, 2004; 279(18): 18342 - 18352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Goon, B. Schilling, M. V. Tullius, B. W. Gibson, and C. R. Bertozzi Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides PNAS, March 18, 2003; 100(6): 3089 - 3094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-H. Chou, T. Hayakawa, S. Diaz, M. Krings, E. Indriati, M. Leakey, S. Paabo, Y. Satta, N. Takahata, and A. Varki Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution PNAS, September 3, 2002; 99(18): 11736 - 11741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Sonnenburg, H. van Halbeek, and A. Varki Characterization of the Acid Stability of Glycosidically Linked Neuraminic Acid. USE IN DETECTING DE-N-ACETYL-GANGLIOSIDES IN HUMAN MELANOMA J. Biol. Chem., May 10, 2002; 277(20): 17502 - 17510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Oetke, R. Brossmer, L. R. Mantey, S. Hinderlich, R. Isecke, W. Reutter, O. T. Keppler, and M. Pawlita Versatile Biosynthetic Engineering of Sialic Acid in Living Cells Using Synthetic Sialic Acid Analogues J. Biol. Chem., February 15, 2002; 277(8): 6688 - 6695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Bertozzi and L. L. Kiessling Chemical Glycobiology Science, March 23, 2001; 291(5512): 2357 - 2364. [Abstract] [Full Text]
|
|
|
|
|
|
O. T. Keppler, R. Horstkorte, M. Pawlita, C. Schmidt, and W. Reutter Biochemical engineering of the N-acyl side chain of sialic acid: biological implications Glycobiology, February 1, 2001; 11(2): 11R - 18R. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Charter, L. K. Mahal, D. E. Koshland Jr., and C. R. Bertozzi Biosynthetic incorporation of unnatural sialic acids into polysialic acid on neural cells Glycobiology, October 1, 2000; 10(10): 1049 - 1056. [Abstract] [Full Text] [PDF]
|
|