Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2000;17(7):485–499. doi: 10.1023/A:1011062223612

Achievements and challenges of sialic acid research

Roland Schauer 1
PMCID: PMC7087979  PMID: 11421344

Abstract

Sialic acids are one of the most important molecules of life, since they occupy the terminal position on macromolecules and cell membranes and are involved in many biological and pathological phenomena. The structures of sialic acids, comprising a family of over 40 neuraminic acid derivatives, have been elucidated. However, many aspects of the regulation of their metabolism at the enzyme and gene levels, as well as of their functions remain mysterious. Sialic acids play a dual role, not only are they indispensable for the protection to and adaptation of life, but are also utilised by life-threatening infectious microorganisms. In this article the present state of knowledge in sialobiology, with an emphasis on my personal experience in this research area, is outlined including a discussion of necessary future work in this fascinating field of cell biology.

Keywords: sialic acid diversity, sialic acid functions, sialic acid future aspects, sialic acid metabolism, sialic acid occurrence

References

  • 1.Gottschalk A, editor. The chemistry and biology of sialic acids and related substances. Cambridge: University Press; 1960. [Google Scholar]
  • 2.Blix G, Gottschalk A, Klenk E. Proposed nomenclature in the field of neuraminic and sialic acids. Nature. 1957;179:1088. doi: 10.1038/1791088b0. [DOI] [PubMed] [Google Scholar]
  • 3.Faillard H, Schauer R. Glycoproteins as lubricants, protective agents, carriers, structural proteins and as participants in other functions. In: Gottschalk A, BBA Library 5, editor. Glycoproteins, Their Composition, Structure and Function. Amsterdam: Elsevier; 1972. pp. 1246–67. [Google Scholar]
  • 4.Klenk E. Neuraminsäure, das Spaltprodukt eines neuen Gehirn-lipoids. Hoppe-Seyler's Z Physiol Chem. 1941;268:50–8. [Google Scholar]
  • 5.Blix G. Ñber die Kohlenhydratgruppen des Submaxillarismucins. Hoppe-Seyler's Z Physiol Chem. 1936;240:43–54. [Google Scholar]
  • 6.Schauer R. Chemistry, metabolism and biological functions of sialic acids. Adv Carbohydr Chem Biochem. 1982;40:131–234. doi: 10.1016/s0065-2318(08)60109-2. [DOI] [PubMed] [Google Scholar]
  • 7.Schauer R, editor. Sialic Acids – Chemistry, Metabolism and Function. Wien/New York: Springer; 1982. [Google Scholar]
  • 8.Schauer R, Kamerling JP. Chemistry, biochemistry and biology of sialic acids. In: Montreuil J, Vliegenthart JFG, Schachter H, editors. Glycoproteins II. Amsterdam: Elsevier; 1997. pp. 243–402. [Google Scholar]
  • 9.Varki A. Diversity in the sialic acids. Glycobiology. 1992;2:25–40. doi: 10.1093/glycob/2.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Schauer R, Faillard H. Zur Wirkungsspezifität der Neuraminidase. Hoppe-Seyler's Z Physiol Chem. 1968;349:961–8. [PubMed] [Google Scholar]
  • 11.Reuter G, Schauer R. Enzymic methods of sialic acid analysis. In: BeMiller JN, Manners DJ, Sturgeon RJ, editors. Methods in Carbohydrate Chemistry. New York: Wiley; 1994. pp. 29–39. [Google Scholar]
  • 12.Kamerling JP, Vliegenthart JFG, Versluis C, Schauer R. Identification of O-acetylated N-acylneuraminic acids by mass spectrometry. Carbohydr Res. 1975;41:7–17. doi: 10.1016/s0008-6215(00)87002-0. [DOI] [PubMed] [Google Scholar]
  • 13.Kamerling JP, Vliegenthart JFG, Schauer R, Strecker G, Montreuil J. Isolation and identification of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid from the urine of a patient with sialuria. Eur J Biochem. 1975;56:253–8. doi: 10.1111/j.1432-1033.1975.tb02228.x. [DOI] [PubMed] [Google Scholar]
  • 14.Zanetta J-P, Timmermann P, Leroy Y. Gas-liquid chromatography of the heptafluorobutyrate derivatives of the O-methylglycosides on capillary columns: a method for the quantitative determination of the monosaccharide composition of glycoproteins and glycolipids. Glycobiology. 1999;9:255–66. doi: 10.1093/glycob/9.3.255. [DOI] [PubMed] [Google Scholar]
  • 15.Hara S, Yamaguchi M, Takemori Y, Furuhata K, Ogura H, Nakamura M. Determination of mono-O-acetylated N-acetyl-neuraminic acids in rat sera by fluorometric high-performance liquid chromatography. Anal Biochem. 1989;179:162–6. doi: 10.1016/0003-2697(89)90218-2. [DOI] [PubMed] [Google Scholar]
  • 16.Shukla AK, Schauer R. Separation of sialic acids by HPLC. Fresenius Z Anal Chem. 1982;311:376. [Google Scholar]
  • 17.Smith H. Questions about the behaviour of bacterial pathogens in vivo. Phil Trans R Soc Lond B. 2000;355:551–64. doi: 10.1098/rstb.2000.0597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Krauß JH, Reuter G, Schauer R, Weckesser J, Mayer H. Sialic acid-containing lipopolysaccharides of purple nonsulfur bacteria. Arch Microbiol. 1988;150:584–9. [Google Scholar]
  • 19.Schauer R, Reuter G, Mühlpfordt H, Andrade AFB, Pereira MEA. The occurrence of N-acetyl-and N-glycolylneuraminic acid in Trypanosoma cruzi. Hoppe-Seyler's Z Physiol Chem. 1983;364:1053–7. doi: 10.1515/bchm2.1983.364.2.1053. [DOI] [PubMed] [Google Scholar]
  • 20.Roth J, Kemp A, Reuter G, Schauer R, Gehring WJ. Occurrence of sialic acids in Drasophila melanogaster. Science. 1992;256:673–5. doi: 10.1126/science.1585182. [DOI] [PubMed] [Google Scholar]
  • 21.Malykh YN, Krisch B, Gerardy-Schahn R, Lapina EB, Shaw L, Schauer R. The presence of N-acetylneuraminic acid in Malpighian tubules of larvae of the cicada Philaenus spumarius. Glycoconjugate J. 1999;16:731–9. doi: 10.1023/a:1007115627708. [DOI] [PubMed] [Google Scholar]
  • 22.Karaçali S, Kirmizigül S, Deveci R, Deveci Ö, Onat T, Gürcü B. Presence of sialic acid in prothoracic glands of Galleria mellonella (Lepidoptera) Tissue & Cell. 1997;29:315–21. doi: 10.1016/s0040-8166(97)80007-9. [DOI] [PubMed] [Google Scholar]
  • 23.Marchal I, Jarvis DL, Cacan R, Verbert A. Glycoproteins from insect cells: sialylated or not? Biol Chem. 2001;382:151–9. doi: 10.1515/BC.2001.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Gowda DC, Reuter G, Schauer R. Structural features of an acidic polysaccharide from the mucin of Drosera binata. Phytochemistry. 1982;21:2297–300. [Google Scholar]
  • 25.Muralikrishna G, Reuter G, Peter-Katalinie J, Egge H, Hanisch F-G, Siebert H-C, Schauer R. Identification of a new ganglioside from the starfish Asterias rubens. Carhohydr Res. 1992;236:321–6. doi: 10.1016/0008-6215(92)85025-u. [DOI] [PubMed] [Google Scholar]
  • 26.Bergwerff AA, Hulleman SD, Kamerling JP, Vliegenthart JFG, Shaw L, Reuter G, Schauer R. Nature and biosynthesis of sialic acids in the starfish Asterias rubens. Biochimie. 1992;74:25–38. doi: 10.1016/0300-9084(92)90181-d. [DOI] [PubMed] [Google Scholar]
  • 27.Kitazume S, Kitajima K, Inoue S, Troy FA, Cho J-W, Lennarz WJ, Inoue Y. Identification of polysialic acid-containing glycoprotein in the jelly coat of sea urchin eggs. Occurrence of a novel type of polysialic acid structure. J Biol Chem. 1994;269:22712–8. [PubMed] [Google Scholar]
  • 28.Kelm S, Schauer R. Sialic acids in molecular and cellular interactions. In: Jeon KW, Jarvik JW, editors. Int Rev Cytology. San Diego: Academic Press; 1997. pp. 137–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Schauer R, Malykh YN, Krisch B, Gollub M, Shaw L. Biosynthesis and biology of N-glycolylneuraminic acid. In: Inoue Y, Lee YC, Troy FA II, editors. Sialobiology and Other Novel Forms of Glycosylation. Osaka: Gakushin Publishing Co.; 1999. pp. 17–27. [Google Scholar]
  • 30.Malykh YN, Krisch B, Shaw L, Warner TG, Sinicropi D, Smith R, Chang J, Schauer R. Distribution and localization of CMP-N-acetylneuraminic acid hydroxylase and N-glycolylneuraminic acid-containing glycoconjugates in porcine lymph node and peripheral blood lymphocytes. Eur J Cell Biol. 2001;80:48–58. doi: 10.1078/0171-9335-00139. [DOI] [PubMed] [Google Scholar]
  • 31.Schauer R, Schoop HJ, Faillard H. Zur Biosynthese der Glykolyl-Gruppe der N-Glykolylneuraminsäure. Hoppe-Seyler's Z Physiol Chem. 1968;349:645–52. [PubMed] [Google Scholar]
  • 32.Shaw L, Schauer R. The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol Chem Hoppe-Seyler. 1988;369:477–86. doi: 10.1515/bchm3.1988.369.1.477. [DOI] [PubMed] [Google Scholar]
  • 33.Gollub M, Schauer R, Shaw L. Cytidine monophosphate-N-acetylneuraminate hydroxylase in the starfish Asterias rubens and other echinoderms. Comp Biochem Physiol Part B. 1998;120:605–15. doi: 10.1016/s0305-0491(98)10058-5. [DOI] [PubMed] [Google Scholar]
  • 34.Lepers A, Shaw L, Schneckenburger P, Cacan R, Verbert A, Schauer R. A study on the regulation of N-glycoloylneuraminic acid biosynthesis and utilization in rat and mouse liver. Eur J Biochem. 1990;193:715–23. doi: 10.1111/j.1432-1033.1990.tb19391.x. [DOI] [PubMed] [Google Scholar]
  • 35.Chou H-H, Takematsu H, Diaz S, Iber J, Nickerson E, Wright KL, Muchmore EA, Nelson DL, Warren ST, Varki A. A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc Natl Acad Sci USA. 1998;95:11751–6. doi: 10.1073/pnas.95.20.11751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Irie A, Koyama S, Kozutsumi Y, Kawasaki T, Suzuki A. The molecular basis for the absence of N-glycolylneuraminic acid in humans. J Biol Chem. 1998;273:15866–71. doi: 10.1074/jbc.273.25.15866. [DOI] [PubMed] [Google Scholar]
  • 37.Schlenzka W, Shaw L, Kelm S, Schmidt CL, Bill E, Trautwein AX, Lottspeich F, Schauer R. CMP-N-acetylneuraminic acid hydroxylase: the first cytosolic Rieske iron-sulphur protein to be described in Eucarya. FEBS Lett. 1996;385:197–200. doi: 10.1016/0014-5793(96)00384-5. [DOI] [PubMed] [Google Scholar]
  • 38.Nöhle U, Beau J-M, Schauer R. Uptake, metabolism and excretion of orally and intravenously administered, double-labeled N-glycoloylneuraminic acid and single-labeled 2-deoxy-2,3-dehydro-N-acetylneuraminic acid in mousse and rat. Eur J Biochem. 1982;126:543–8. doi: 10.1111/j.1432-1033.1982.tb06815.x. [DOI] [PubMed] [Google Scholar]
  • 39.Nöhle U, Schauer R. Metabolism of sialic acids from exogeneously administered sialyllactose and mucin in mouse and rat. Hoppe-Seyler's Z Physiol Chem. 1984;365:1457–67. doi: 10.1515/bchm2.1984.365.2.1457. [DOI] [PubMed] [Google Scholar]
  • 40.Tangvoranuntakul P, Gagneux P, Diaz S, Varki N, Muchmore E, Varki A, Expression of N-glycolyl-neuraminic acid in normal, fetal and malignant human tissues, Glycobiology10, abstract 53, in press (2000).
  • 41.Schauer R, Schmid H, Pommerencke J, Iwersen M, Kohla G. Metabolism and role of O-acetylated sialic acids. In: Wu AM, editor. Molecular Immunology of Complex Carbohydrates 2. New York: Plenum; 2001. pp. 325–42. [DOI] [PubMed] [Google Scholar]
  • 42.Schauer R. Biosynthese von N-Acetyl-O-Acetylneuraminsäuren I. Hoppe-Seyler's Z Physiol Chem. 1970;351:595–602. [PubMed] [Google Scholar]
  • 43.Iwersen M, Vandamme-Feldhaus V, Schauer R. Enzymatic 4-Oacetylation of N-acetylneuraminic acid in guinea-pig liver. Glycoconjugate J. 1998;15:895–904. doi: 10.1023/a:1006911100081. [DOI] [PubMed] [Google Scholar]
  • 44.Butor C, Diaz S, Varki A. High level O-acetylation of sialic acids on N-linked oligosaccharides of rat liver membranes. J Biol Chem. 1993;268:10197–206. [PubMed] [Google Scholar]
  • 45.Vandamme-Feldhaus V, Schauer R. Characterization of the enzymatic 7-O-acetylation of sialic acids and evidence for enzymatic O-acetyl migration from C-7 to C-9 in bovine submandibular glands. J Biochem (Tokyo) 1998;124:111–21. doi: 10.1093/oxfordjournals.jbchem.a022069. [DOI] [PubMed] [Google Scholar]
  • 46.Kamerling JP, Schauer R, Shukla AK, Stoll S, van Halbeek H, Vliegenthart JFG. Migration of O-acetyl groups in N,O-acetylneuraminic acids. Eur J Biochem. 1987;162:601–7. doi: 10.1111/j.1432-1033.1987.tb10681.x. [DOI] [PubMed] [Google Scholar]
  • 47.Shi WX, Chammas R, Varki A. Induction of sialic acid 9-O-acetylation by diverse gene products: implications for the expression cloning of sialic acid O-acetyltransferases. Glycobiology. 1998;8:199–205. doi: 10.1093/glycob/8.2.199. [DOI] [PubMed] [Google Scholar]
  • 48.Kelm A, Shaw L, Schauer R, Reuter G. The biosynthesis of 8-O-methylated sialic acids in the starfish Asterias rubens. Eur J Biochem. 1998;251:874–84. doi: 10.1046/j.1432-1327.1998.2510874.x. [DOI] [PubMed] [Google Scholar]
  • 49.Kochetkov NK, Smirnova GP, Chekareva NV. Isolation and structural studies of a sulfated sialosphingolipid from the sea urchin Echinocardium cordatum. Biochim Biophys Acta. 1976;424:274–83. doi: 10.1016/0005-2760(76)90195-8. [DOI] [PubMed] [Google Scholar]
  • 50.Schauer R. Biochemistry of sialic acid diversity. In: Ernst B, Hart GW, Sinaÿ P, editors. Carbohydrates in Chemistry and Biology. Weinheim: Wiley-VCH; 2000. pp. 227–43. [Google Scholar]
  • 51.Schmelter T, Ivanov S, Wember M, Stangier P, Thiem J, Schauer R. Partial purification and characterization of cytidine-5'-monophosphosialate synthase from rainbow trout liver. Biol Chem Hoppe-Seyler. 1993;374:337–42. doi: 10.1515/bchm3.1993.374.1-6.337. [DOI] [PubMed] [Google Scholar]
  • 52.Kleineidam RG, Hofmann O, Reuter G, Schauer R. Indications for the enzymic synthesis of 9-O-lactoyl-N-acetylneuraminic acid in equine liver. Glycoconjugate J. 1993;10:116–9. doi: 10.1007/BF00731195. [DOI] [PubMed] [Google Scholar]
  • 53.Chammas R, Sonnenburg JL, Watson NE, Tai T, Farquhar MG, Varki NM, Varki A. De-N-acetyl-gangliosides in humans: unusual subcellular distribution of a novel tumor antigen. Cancer Res. 1999;59:1337–46. [PubMed] [Google Scholar]
  • 54.Nakamura T, Urashima T, Nakagawa M, Saito T. Sialyllactose occurs as free lactones in ovine colostrum. Biochim Biophys Acta. 1998;1381:286–92. doi: 10.1016/s0304-4165(98)00040-3. [DOI] [PubMed] [Google Scholar]
  • 55.Traving C, Schauer R. Structure, function and metabolism of sialic acids. Cell Mol Life Sci. 1998;54:1330–49. doi: 10.1007/s000180050258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Roggentin P, Rothe B, Kaper JB, Galen L, Lawrisuk L, Vimr ER, Schauer R. Conserved sequences in bacterial and viral sialidases. Glycoconjugate J. 1989;6:349–53. doi: 10.1007/BF01047853. [DOI] [PubMed] [Google Scholar]
  • 57.Roggentin P, Schauer R, Hoyer LL, Vimr ER. The sialidase superfamily and its spread by horizontal gene transfer. Mol Microbiol. 1993;9:915–21. doi: 10.1111/j.1365-2958.1993.tb01221.x. [DOI] [PubMed] [Google Scholar]
  • 58.Corfield T. Bacterial sialidases–roles in pathogenicity and nutrition. Glycobiology. 1992;6:509–21. doi: 10.1093/glycob/2.6.509. [DOI] [PubMed] [Google Scholar]
  • 59.Roggentin T, Kleineidam RG, Majewski DM, Tirpitz D, Roggentin P, Schauer R. An immunoassay for the rapid and specific detection of three sialidase-producing Clostridia causing gas gangrene. J Immunol Methods. 1993;157:125–33. doi: 10.1016/0022-1759(93)90078-l. [DOI] [PubMed] [Google Scholar]
  • 60.Kleineidam RG, Furuhata K, Ogura H, Schauer R. 4-Methylumbelliferyl-α-glycosides of partially O-acetylated N-acetylneuraminic acids as substrates of bacterial and viral sialidases. Biol Chem Hoppe-Seyler. 1990;371:715–9. doi: 10.1515/bchm3.1990.371.2.715. [DOI] [PubMed] [Google Scholar]
  • 61.von Itzstein M, Thomson RJ. The synthesis of noval sialic acids as biological probes. In: Driguez H, Thiem J, editors. Topics in Current Chemistry. Berlin, Heidelberg: Springer; 1997. pp. 119–70. [Google Scholar]
  • 62.Schenkman S, Jiang MS, Hart GW, Nussenzweig V. A novel cell surface transsialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells. Cells. 1991;65:1117–25. doi: 10.1016/0092-8674(91)90008-m. [DOI] [PubMed] [Google Scholar]
  • 63.Previato JO, Andrade AF, Pessolani MC, Mendonca-Previato L. Incorporation of sialic acid into Trypanasoma cruzi macromolecules. Mol Biochem Parasitol. 1985;16:85–96. doi: 10.1016/0166-6851(85)90051-9. [DOI] [PubMed] [Google Scholar]
  • 64.Engstler M, Reuter G, Schauer R. Purification and characterization of a novel sialidase in procyclic culture forms of Trypanosoma brucei. Mol Biochem Parasitol. 1992;54:21–30. doi: 10.1016/0166-6851(92)90091-w. [DOI] [PubMed] [Google Scholar]
  • 65.Buschiazzo A, Tavares GA, Campetella O, Spinelli S, Cremona ML, Pari<q>s G, Fernanda Amaya M, Frasch ACC, Alzari PM. Structural basis of sialyltransferase activity in trypanosomal sialidases. The Embo J. 2000;19:16–24. doi: 10.1093/emboj/19.1.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Reuter G, Schauer R, Prioli R, Pereira MEA. Isolation and properties of a sialidase from Trypanosoma rangeli. Glycoconjugate J. 1987;4:339–48. [Google Scholar]
  • 67.Smith LE, Eichinger D. Directed mutagenesis of the Trypanosoma cruzi trans-sialidase enzyme identifies two domains involved in its sialyltransferase activity. Glycobiology. 1997;7:445–51. doi: 10.1093/glycob/7.3.445. [DOI] [PubMed] [Google Scholar]
  • 68.Engstler M, Schauer R, Brun R. Distribution and developmentally regulated trans-sialidases in the Kinetoplastida and characterization of a shed trans-sialidase activity from procyclic Trypanosoma congolense. Acta Tropica. 1995;59:117–29. doi: 10.1016/0001-706x(95)00077-r. [DOI] [PubMed] [Google Scholar]
  • 69.Pereira-Chioccola VL, Schenkman S. Biological role of Trypanosoma cruzi trans-sialidase. Biochem Soc Trans. 1999;27:516–8. doi: 10.1042/bst0270516. [DOI] [PubMed] [Google Scholar]
  • 70.Carrillo MB, Gao W, Herrera M, Alroy J, Moore JB, Beverley SM, Pereira MA. Heterologous expression of Trypanosoma cruzi trans-sialidase in Leishmania major enhances virulence. Infect Immun. 2000;68:2728–34. doi: 10.1128/iai.68.5.2728-2734.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Tertov VV, Kaplun VV, Sobenin IA, Orekhov AN. Low-density Lipoprotein modification occurring in human plasma. Possible mechanism of in vivo lipoprotein desialylation as a primary step of atherogenic modification. Atherosclerosis. 1998;138:183–95. doi: 10.1016/s0021-9150(98)00023-9. [DOI] [PubMed] [Google Scholar]
  • 72.Chou M-Y, Li S-C, Li Y-T. Cloning and expression of sialidase L, a NeuAc?2-3Gal-specific sialidase from the leech, Macrobdella decora. J Biol Chem. 1996;271:19219–24. doi: 10.1074/jbc.271.32.19219. [DOI] [PubMed] [Google Scholar]
  • 73.Hasegawa T, Yamaguchi K, Wada T, Takeda A, Itoyama Y, Miyagi T. Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation. J Biol Chem. 2000;275:8007–15. doi: 10.1074/jbc.275.11.8007. [DOI] [PubMed] [Google Scholar]
  • 74.Kleineidam RG, Kruse S, Roggentin P, Schauer R. Elucidation of the role of functional amino acid residues of the 'small’ sialidase from Clostridium perfringens by site-directed mutagenesis. Biol Chem. 2001;382:313–9. doi: 10.1515/BC.2001.038. [DOI] [PubMed] [Google Scholar]
  • 75.Schauer R, Sommer U, Kruger D, van Unen H, Traving C. The terminal enzymes of sialic acid metabolism: Acylneuraminate pyruvate-lyases. Bioscience Reports. 1999;19:373–83. doi: 10.1023/a:1020256004616. [DOI] [PubMed] [Google Scholar]
  • 76.Izard T, Lawrence MC, Malby RL, Lilley GG, Colman PM. The three-dimensional structure of N-acetylneuraminate lyase from Escherichia coli. Structure. 1994;2:361–9. doi: 10.1016/s0969-2126(00)00038-1. [DOI] [PubMed] [Google Scholar]
  • 77.Sander M, Veh RW, Schauer R. Partial purification and further characterization of glycoprotein-specific neuraminidase from horse liver. In: Schauer R, Boer P, Buddecke E, Kramer MF, Vliegenthart JFG, Wiegandt H, editors. Glycoconjugates, Proc Fifth Int Symp Glycoconjugates. Stuttgart: Georg Thieme Publ; 1979. pp. 44–5. [Google Scholar]
  • 78.Schauer R, Reuter G, Stoll S. Sialate-O-acetylesterases: key enzymes in sialic acid catabolism. Biochimie. 1988;70:1511–9. doi: 10.1016/0300-9084(88)90288-x. [DOI] [PubMed] [Google Scholar]
  • 79.Herrler U, Rott R, Klenk H-D, Müller H-P, Shukla AK, Schauer R. The receptor destroying enzyme of influenza C virus is neuraminate-O-acetylesterase. EMBO J. 1985;4:1503–6. doi: 10.1002/j.1460-2075.1985.tb03809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Rosenthal PB, Zhang X, Formanowski F, Fitz W, Wong C-H, Meier-Ewert H, Skehel JJ, Wiley DC. Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus. Nature. 1998;396:92–6. doi: 10.1038/23974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Hubl U, Ishida H, Kiso M, Hasegawa A, Schauer R. Studies on the specificity and sensitivity of the influenza C virus binding assay for O-acetylated sialic acids and its application to human melanomas. J Biochem. 2000;27:1021–31. doi: 10.1093/oxfordjournals.jbchem.a022693. [DOI] [PubMed] [Google Scholar]
  • 81a.Fahr C, Schauer R. Detection of sialic acids and gangliosides with special reference to 9-O-acetylated species in basaliomas and normal human skin. J Invest Dermatol. 2001;116:254–60. doi: 10.1046/j.1523-1747.2001.01237.x. [DOI] [PubMed] [Google Scholar]
  • 82.Regl G, Kaser A, Iwersen M, Schmid H, Kohla G, Strobl B, Vilas U, Schauer R, Vlasak R. The hemagglutinin-esterase of mouse hepatitis virus strain S is a sialate-4-O-acetylesterase. J Virol. 1999;73:4721–7. doi: 10.1128/jvi.73.6.4721-4727.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Mitsuoka C, Ohmori K, Kimura N, Kanamori A, Komba S, Ishida H, Kiso M, Kannagi R. Regulation of selectin binding activity by cyclization of sialic acid moiety of carbohydrate ligands on human leukocytes. Proc Natl Acad Sci USA. 1999;96:1597–602. doi: 10.1073/pnas.96.4.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Schauer R. Sialic acids and their roles as biological masks. Trends Biochem Sci. 1985;10:357–60. [Google Scholar]
  • 85.Siebert H-C, von der Lieth C-W, Dong X, Reuter G, Schauer R, Gabius H-J, Vliegenthart JFG. Molecular dynamics-derived conformation and intramolecular interaction analysis of the N-acetyl-9-O-acetylneuraminic acid-containing GDIa and NMR-based analysis of its binding to a human polyclonal immunoglobulin G fraction with selectivity for O-acetylated sialic acids. Glycobiology. 1996;6:561–72. doi: 10.1093/glycob/6.6.561-b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Ashwell G, Morell AG. The role of surface carbohydrates in the hepatic recognition and transport circulating glycoproteins. Adv Enzymol. 1974;41:99–128. doi: 10.1002/9780470122860.ch3. [DOI] [PubMed] [Google Scholar]
  • 87.Jancik J, Schauer R. Sialic acid – a determinant of the life-time of rabbit erythrocytes. Hoppe-Seyler's Z Physiol Chem. 1974;355:395–400. doi: 10.1515/bchm2.1974.355.1.395. [DOI] [PubMed] [Google Scholar]
  • 88.Müller E, Schröder C, Sharon N, Schauer R. Binding and phagocytosis of sialidase-treated rat erythrocytes by a mechanism independent of opsonins. Hoppe-Seyler's Z Physiol Chem. 1983;364:1410–20. doi: 10.1515/bchm2.1983.364.2.1419. [DOI] [PubMed] [Google Scholar]
  • 89.Bratosin D, Mazurier J, Tissier JP, Estaquier J, Huart JJ, Ameisen JC, Aminoff D, Montreuil J. Cellular and molecular mechanisms of senescent erythrocyte phagocytosis by macrophages. Biochimie. 1998;80:173–95. doi: 10.1016/s0300-9084(98)80024-2. [DOI] [PubMed] [Google Scholar]
  • 90.Fischer C, Kelm S, Ruch B, Schauer R. Reversible binding of sialidase-treated rat lymphocytes by homologous peritoneal macrophages. Carbohydr Res. 1991;213:263–73. doi: 10.1016/s0008-6215(00)90613-x. [DOI] [PubMed] [Google Scholar]
  • 91.Varki A. Sialic acids as ligands in recognition phenomena. The FASEB J. 1997;11:248–55. doi: 10.1096/fasebj.11.4.9068613. [DOI] [PubMed] [Google Scholar]
  • 92.Lee H, Kelm S, Michalski J-C, Schauer R. Influence of sialic acids on the galactose-recognizing receptor of rat peritoneal macrophages. Biol Chem Hoppe-Seyler. 1990;371:307–16. doi: 10.1515/bchm3.1990.371.1.307. [DOI] [PubMed] [Google Scholar]
  • 93.Crocker PR, Kelm S, Dubois C, Martin B, McWilliam AS, Shotton DM, Paulson JC, Gordon S. Purification and properties of sialoadhesin, a sialic acid-binding receptor of murine tissue macrophages. EMBO J. 1991;10:1661–9. doi: 10.1002/j.1460-2075.1991.tb07689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Crocker PR, Clark EA, Filbin M, Gordon S, Jones Y, Kehrl JH, Kelm S, Le Douarin N, Powell L, Roder J, Schnaar RL, Sgroi DC, Stamenkovic I, Schauer R, Schachner M, van den Berg T.K., Watt SM, Varki A. Siglecs: a family of sialic-acid binding lectins. Glycobiology. 1998;8:V–VI. doi: 10.1093/oxfordjournals.glycob.a018832. [DOI] [PubMed] [Google Scholar]
  • 95.Kelm S, Brossmer R, Isecke R, Groß H-J, Strenge K, Schauer R. Functional groups of sialic acids involved in binding to siglecs (sialoadhesins) deduced from interactions with synthetic analogues. Eur J Biochem. 1998;255:663–72. doi: 10.1046/j.1432-1327.1998.2550663.x. [DOI] [PubMed] [Google Scholar]
  • 96.Brinkman-Van der Linden ECM, Sjoberg ER, Juneja LR, Crocker PR, Varki N, Varki A. Loss of N-glycolylneuraminic acid in human evolution. J Biol Chem. 2000;275:8633–40. doi: 10.1074/jbc.275.12.8633. [DOI] [PubMed] [Google Scholar]
  • 97.Kelm S, Pelz A, Schauer R, Filbin MT, Tang S, de Bellard M-E, Schnaar RL, Mahoney JA, Hartnell A, Bradfield P, Crocker PR. Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily. Curr Biol. 1994;4:965–72. doi: 10.1016/s0960-9822(00)00220-7. [DOI] [PubMed] [Google Scholar]
  • 98.Mann B, Klussmann E, Vandamme-Feldhaus V, Iwersen M, Hanski M-L, Riecken E-O, Buhr HJ, Schauer R, Kim YS, Hanski C. Low O-acetylation of sialyl-Lex contributes to its overexpression in colon carcinoma metastases. Int J Cancer. 1997;72:258–64. doi: 10.1002/(sici)1097-0215(19970717)72:2<258::aid-ijc10>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  • 99.Hirmo S, Kelm S, Iwersen M, Hotta K, Goso Y, Ishihara K, Suguri T, Morita M, Wadström T, Schauer R. Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human gastrointestinal mucins and milk glycoproteins. FEMS Immunol Med Microbiol. 1998;20:275–81. doi: 10.1016/S0928-8244(98)00022-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100.Castillo C, Diaz ME, Balbi D, Thornhill WB, Recio-Pinto E. Changes in sodium channel function during postnatal brain development reflect increases in the level of channel sialidation. Developmental Brain Res. 1997;104:119–30. doi: 10.1016/s0165-3806(97)00159-4. [DOI] [PubMed] [Google Scholar]
  • 101.Brückner K, Perez L, Clausen H, Cohen S. Glycosyltransferase activity of Fringe modulates Notch-Delta interactions. Nature. 2000;406:411–5. doi: 10.1038/35019075. [DOI] [PubMed] [Google Scholar]
  • 102.Schauer R, Stoll S, Reuter G. Differences in the amount of N-acetyl-and N-glycoloyl-neuraminic acids, as well as O-acetylated sialic acids, of fetal and adult bovine tissues. Carbohydr Res. 1991;213:353–9. doi: 10.1016/s0008-6215(00)90623-2. [DOI] [PubMed] [Google Scholar]
  • 103.Muchmore EA. Developmental sialic acid modifications in rat organs. Glycobiology. 1992;4:337–43. doi: 10.1093/glycob/2.4.337. [DOI] [PubMed] [Google Scholar]
  • 104.Herrler G, Reuter G, Rott R, Klenk H-D, Schauer R. N-Acetyl-9-O-acetylneuraminic acid, the receptor determinant for influenza C virus, is a differentiation marker on chicken erythrocytes. Biol Chem Hoppe-Seyler. 1987;368:451–4. doi: 10.1515/bchm3.1987.368.1.451. [DOI] [PubMed] [Google Scholar]
  • 105.Matthijs G. Carbohydrate-deficient glycoprotein syndromes become congenital disorders of glycosylation: an updated nomenclature for CDG. Glycocojugate J. 1999;16:669–71. doi: 10.1023/a:1017249723165. [DOI] [PubMed] [Google Scholar]
  • 106.Salhanick A., Amatruda JM. Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus. Am J Physiol. 1988;255:E173–9. doi: 10.1152/ajpendo.1988.255.2.E173. [DOI] [PubMed] [Google Scholar]
  • 107.Sillanaukee P, Pönniö M, Seppä K. Sialic acid: new potential marker of alcohol abuse. Alcohol Clin Exp Res. 1999;23:1039–43. doi: 10.1111/j.1530-0277.1999.tb04222.x. [DOI] [PubMed] [Google Scholar]
  • 108.Ghosh P, Ender I, Hale EA. Long-term ethanol consumption selectively impairs ganglioside pathway in rat brain. Alcohol Clin Exp Res. 1998;22:1220–6. [PubMed] [Google Scholar]
  • 108a.Zuegg J, Gready JE. Molecular dynamics simulation of human prion protein including both N-linked oligosaccharides and the GPI anchor. Glycobiology. 2000;10:959–74. doi: 10.1093/glycob/10.10.959. [DOI] [PubMed] [Google Scholar]
  • 109.Horstkorte R, Nöhring S, Wiechens N, Schwarzkopf M, Danker K, Reutter W, Lucka L. Tissue expression and amino acid sequence of murine UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase. Eur J Biochem. 1999;260:923–7. doi: 10.1046/j.1432-1327.1999.00253.x. [DOI] [PubMed] [Google Scholar]
  • 110.Brand Miller J, McVeagh P. Human milk oligosaccharides: 130 reasons to breast-feed. British J Nutrition. 1999;82:333–5. doi: 10.1017/s0007114599001567. [DOI] [PubMed] [Google Scholar]
  • 111.Engfer MB, Stahl B, Finke B, Sawatzki G, Daniel H. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000;71:1589–96. doi: 10.1093/ajcn/71.6.1589. [DOI] [PubMed] [Google Scholar]
  • 112.Kikuchi K, Kikuchi H, Tsuiki S. Activities of sialic acidsynthesizing enzymes in rat liver and rat and mouse tumors. Biochim Biophys Acta. 1971;252:357–68. doi: 10.1016/0304-4165(71)90017-1. [DOI] [PubMed] [Google Scholar]
  • 113.Georgopoulou N, Breen KC. Overexpression of ?2,3 sialyltransferase in neuroblastoma cells results in an upset in the glycosylation process. Glycoconjugate J. 1999;16:649–57. doi: 10.1023/a:1007033218309. [DOI] [PubMed] [Google Scholar]
  • 114.Krause T, Turner GA. Are selectins involved in metastasis? Clin Exp Metastasis. 1999;17:183–92. doi: 10.1023/a:1006626500852. [DOI] [PubMed] [Google Scholar]
  • 115.Kleineidam RG, Schmelter T, Schwarz RT, Schauer R. Studies on the inhibition of sialyl-and galactosyltransferases. Glycoconjugate J. 1997;14:57–66. doi: 10.1023/a:1018560931389. [DOI] [PubMed] [Google Scholar]
  • 116.Dufner G, SchwoÈrer R, Müller B, Schmidt RR, Base-and sugar-modified cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac) analogues–synthesis and studies with ?(2–6)-sialyltransferase from rat liver, Eur J Org Chem 1467–82 (2000).
  • 117.Rudd PM, Wormald MR, Dwek RA. Glycosylation and the immune system. Trends Glycosci Glycotechnol. 1999;11:1–21. [Google Scholar]
  • 118.Tanemura M, Miyagawa S, Koyota S, Koma M, Matsuda H, Tsuji S, Shirakura R, Taniguchi N. Reduction of the major swine xenoantigen, the ?-galactosyl epitope by transfection of the ?2,3-sialyltransferase gene. J Biol Chem. 1998;273:16421–5. doi: 10.1074/jbc.273.26.16421. [DOI] [PubMed] [Google Scholar]
  • 119.Mühlenhoff M, Eckhardt M, Gerardy-Schahn R. Polysialic acid: three-dimensional structure, biosynthesis and function. Current Opinion Struct Biol. 1998;8:558–64. doi: 10.1016/s0959-440x(98)80144-9. [DOI] [PubMed] [Google Scholar]
  • 120.Angata K, Suzuki M, McAuliffe J, Ding Y, Hindsgaul O, Fukuda M. Differential biosynthesis of polysialic acid on neural cell adhesion molecule (NCAM) and oligosaccharide acceptors by three distinct ?2,8-sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8SiaIII. J Biol Chem. 2000;275:18594–601. doi: 10.1074/jbc.M910204199. [DOI] [PubMed] [Google Scholar]
  • 121.Aoki K, Nakahara Y, Yarnada S, Eto K. Role of polysialic acid on outgrowth of rat olfactory receptor neurons. Mechan Develop. 1999;85:103–10. doi: 10.1016/s0925-4773(99)00092-1. [DOI] [PubMed] [Google Scholar]

Articles from Glycoconjugate Journal are provided here courtesy of Nature Publishing Group

RESOURCES