A small-molecule modulator of poly-α2,8-sialic acid expression on cultured neurons and tumor cells

被引:87
作者
Mahal, LK
Charter, NW
Angata, K
Fukuda, M
Koshland, DE
Bertozzi, CR [1 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[4] Burnham Inst, Ctr Canc Res, Glycobiol Program, La Jolla, CA 92037 USA
关键词
D O I
10.1126/science.1062192
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 rote complementary to genetic and biochemical approaches in the study of complex PSA-mediated events.
引用
收藏
页码:380 / 382
页数:3
相关论文
共 27 条
  • [1] Differential and cooperative polysialylation of the neural cell adhesion molecule by two polysialyltransferases, PST and STX
    Angata, K
    Suzuki, M
    Fukuda, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (43) : 28524 - 28532
  • [2] Human STX polysialyltransferase forms the embryonic form of the neural cell adhesion molecule - Tissue-specific expression, neurite outgrowth, and chromosomal localization in comparison with another polysialyltransferase, PST
    Angata, K
    Nakayama, J
    Fredette, B
    Chong, K
    Ranscht, B
    Fukuda, M
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (11) : 7182 - 7190
  • [3] Chemical glycobiology
    Bertozzi, CR
    Kiessling, LL
    [J]. SCIENCE, 2001, 291 (5512) : 2357 - 2364
  • [4] CRACKING THE CARBOHYDRATE CODE FOR SELECTIN RECOGNITION
    BERTOZZI, CR
    [J]. CHEMISTRY & BIOLOGY, 1995, 2 (11): : 703 - 708
  • [5] Synthesis of CMP-sialic acid conjugates: Substrates for the enzymatic synthesis of natural and designed sialyl oligosaccharides
    Chappell, MD
    Halcomb, RL
    [J]. TETRAHEDRON, 1997, 53 (32) : 11109 - 11120
  • [6] Biosynthetic incorporation of unnatural sialic acids into polysialic acid on neural cells
    Charter, NW
    Mahal, LK
    Koshland, DE
    Bertozzi, CR
    [J]. GLYCOBIOLOGY, 2000, 10 (10) : 1049 - 1056
  • [7] MOLECULAR CHARACTERIZATION OF EUKARYOTIC POLYSIALYLTRANSFERASE-1
    ECKHARDT, M
    MUHLENHOFF, M
    BETHE, A
    KOOPMAN, J
    FROSCH, M
    GERARDYSCHAHN, R
    [J]. NATURE, 1995, 373 (6516) : 715 - 718
  • [8] Mice deficient in the polysialyltransferase ST8SialV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity
    Eckhardt, M
    Bukalo, O
    Chazal, G
    Wang, LH
    Goridis, C
    Schachner, M
    Gerardy-Schahn, R
    Cremer, H
    Dityatev, A
    [J]. JOURNAL OF NEUROSCIENCE, 2000, 20 (14) : 5234 - 5244
  • [9] Fukuda M, 1996, CANCER RES, V56, P2237
  • [10] Hildebrandt H, 1998, CANCER RES, V58, P779