Abstract
Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). Inhibition occurs through a metabolic mechanism in which ManBut is converted to unnatural sialic acid derivatives that effectively act as chain terminators during cellular PSA biosynthesis. N-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Carbohydrate Conformation
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Cell Membrane / metabolism*
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HeLa Cells
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Hexosamines / metabolism
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Hexosamines / pharmacology*
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Humans
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Microscopy, Fluorescence
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Neural Cell Adhesion Molecules / genetics
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Neural Cell Adhesion Molecules / metabolism
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Neurons / metabolism*
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Recombinant Fusion Proteins / metabolism
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Sialic Acids / biosynthesis*
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Sialic Acids / chemistry
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Sialyltransferases / genetics
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Sialyltransferases / metabolism
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Transfection
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Tumor Cells, Cultured
Substances
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Hexosamines
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N-butanoylmannosamine
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Neural Cell Adhesion Molecules
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Recombinant Fusion Proteins
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Sialic Acids
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alpha(2-8)polysialic acid
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N-propanoylmannosamine
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CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase
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Sialyltransferases