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Science 12 October 2001:
Vol. 294. no. 5541, pp. 380 - 381
DOI: 10.1126/science.1062192
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Reports

A Small-Molecule Modulator of Poly-alpha 2,8-Sialic Acid Expression on Cultured Neurons and Tumor Cells

Lara K. Mahal,1 Neil W. Charter,2 Kiyohiko Angata,4 Minoru Fukuda,4 Daniel E. Koshland Jr.,2 Carolyn R. Bertozzi123*

Poly-alpha 2,8-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.

1 Department of Chemistry,
2 Department of Molecular and Cell Biology,
3 Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
4 Glycobiology Program, Cancer Research Center, Burnham Institute, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: bertozzi{at}cchem.berkeley.edu

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