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

Brian E. Collins, Thomas J. Fralich, Saki Itonori, Yoshitaka Ichikawa, Ronald Lee Schnaar

Research output: Contribution to journalArticle

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)11-20
Number of pages10
JournalGlycobiology
Volume10
Issue number1
StatePublished - Jan 2000

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Myelin-Associated Glycoprotein
N-Acetylneuraminic Acid
Sialic Acids
Lectins
Nerve Regeneration
Neurons
Bearings (structural)
Glycoconjugates
Hybrid Cells
Gangliosides
Neuroblastoma
Glioma
N-glycolylneuraminic acid
N-glycolylmannosamine pentaacetate
Glycoproteins
Cells
Wounds and Injuries

Keywords

  • N-acetylmannosamine
  • N-acetylneuraminic acid
  • N-glycolylneuraminic acid
  • Sialic acid biosynthesis
  • Siglec recognition

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "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",
abstract = "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. 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.",
keywords = "N-acetylmannosamine, N-acetylneuraminic acid, N-glycolylneuraminic acid, Sialic acid biosynthesis, Siglec recognition",
author = "Collins, {Brian E.} and Fralich, {Thomas J.} and Saki Itonori and Yoshitaka Ichikawa and Schnaar, {Ronald Lee}",
year = "2000",
month = "1",
language = "English (US)",
volume = "10",
pages = "11--20",
journal = "Glycobiology",
issn = "0959-6658",
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TY - JOUR

T1 - Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate

T2 - Inhibition of myelin-associated glycoprotein binding to neural cells

AU - Collins, Brian E.

AU - Fralich, Thomas J.

AU - Itonori, Saki

AU - Ichikawa, Yoshitaka

AU - Schnaar, Ronald Lee

PY - 2000/1

Y1 - 2000/1

N2 - 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. 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.

AB - 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. 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.

KW - N-acetylmannosamine

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M3 - Article

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