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Chemical Compound Review

Sialic acids     5-acetamido-4,6,7,8,9- pentahydroxy-2-oxo...

Synonyms: NSC-409925, AC1L8BHK, NSC409925
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Disease relevance of sialic acid

  • The three-dimensional structures of influenza virus haemagglutinins complexed with cell receptor analogues show sialic acids bound to a pocket of conserved amino acids surrounded by antibody-binding sites [1].
  • Finally, as compounds coating the surfaces of virtually every vertebrate cell, sialic acids provide information about the host environment that, at least in Escherichia coli, is interpreted by the global regulator encoded by nanR [2].
  • Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs [3].
  • Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave alpha2,3-linked sialic acids from glycoconjugates [4].
  • Binding was also diminished when neutrophils were treated with neuraminidase from Vibrio cholerae, which cleaves alpha 2-3-, alpha 2-6-, and alpha 2-8-linked sialic acids, or from Newcastle disease virus, which cleaves only alpha 2-3- and alpha 2-8-linked sialic acids [5].

High impact information on sialic acid


Chemical compound and disease context of sialic acid

  • These results suggest that both the linkage and expression levels of the terminal sialic acids of alpha3beta1 integrin N-glycans play an important role in glioma cell-extracellular matrix interactions [8].
  • Human influenza A virus hemagglutinin distinguishes sialyloligosaccharides in membrane-associated gangliosides as its receptor which mediates the adsorption and fusion processes of virus infection. Specificity for oligosaccharides and sialic acids and the sequence to which sialic acid is attached [9].
  • In the accompanying paper (Shi, W.-X., Chammas, R., and Varki, A. (1996) J. Biol. Chem. 261, 31517-31525), we report that the extent of 9-O-acetylation of cell surface sialic acids on murine erythroleukemia (MEL) cells can be modified by various manipulations, including differentiation, nocodazole treatment, and 9-O-acetyl esterase treatment [10].
  • Influenza A virus specificity for the host is mediated by the viral surface glycoprotein hemagglutinin (HA), which binds to receptors containing glycans with terminal sialic acids [11].
  • Herpes simplex virus type 1 (HSV-1) envelope proteins are posttranslationally modified by the addition of sialic acids to the termini of the glycan side chains [12].

Biological context of sialic acid

  • It has also been implicated in cell adhesion through recognition of alpha2,6-linked sialic acids on glycans of target cells [13].
  • An autosomal dominant gene regulates the extent of 9-O-acetylation of murine erythrocyte sialic acids. A probable explanation for the variation in capacity to activate the human alternate complement pathway [14].
  • Cell surface-located sialic acids of the capsule and the lipooligosaccharide (LOS) are both pivotal virulence factors in Neisseria meningitidis, promoting survival and dissemination of this pathogen which can cause both sepsis and meningitis [15].
  • Advances made in recent years that 'humanize' plant glycosylation pathways combined with the discovery of terminal sialic acids (SAs) in plants now make feasible the bioengineering in plants of glycoproteins that have mammalian-like glycosylation [16].
  • The glycosidic linkage of sialic acids is much more sensitive to acid hydrolysis than those of other monosaccharides in vertebrates [17].

Anatomical context of sialic acid

  • The sialic acids are indispensable for the function of VAP-1, since the desialylated form of VAP-1 no longer mediates lymphocyte binding [18].
  • Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation [3].
  • Incubation of liver endothelium with double-labeled TF (sialic acids with 3H and protein core with 125I or 59Fe) led initially to a concordant uptake of the two labels, which were then dissociated and 3H was retained by the cell [19].
  • Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids [20].
  • Experiments to block adhesion by pretreatment of cells with either neuraminidase or mucin show that the sialic acids-rich moiety is on the nerve cells, while its receptor is on the muscle fibers [21].

Associations of sialic acid with other chemical compounds

  • Removal of terminal sialic acids with neuraminidase or protease treatment of cells abrogated cell adhesion to both selectin substrates [22].
  • However, after mild acid treatment to remove sialic acids and fucose, releasable TF antigen was increased in all nine of these histologically normal mucin samples (5.5 +/- 2.6 ng/micrograms protein, P < 0.0002) [23].
  • The nature of the intraindividual biochemical variation can be explained by differences in sialic acid content because after digestion with neuraminidase the terminal sialic acids are removed to yield a single major band corresponding to the C1R polypeptide [24].
  • The patterns of mRNA expression were compared with the pattern of binding of two sialic acid-specific plant lectins, Sambucus nigra agglutinin and Maackia amurensis agglutinin, which preferentially recognize alpha 2,6- and alpha 2,3-linked sialic acids, respectively, on N-glycans [25].
  • This glycoprotein contains < 1% of the total membrane-bound sialic acids and a very small fraction of the total SLex on neutrophil membranes [26].

Gene context of sialic acid

  • In TAP1-deficient, HLA-B27 transgenic animals, HLA-B27 molecules fail to assemble correctly, and do not undergo carbohydrate modifications associated with the Golgi apparatus, such as conversion to Endoglycosidase H resistance, and acquisition of sialic acids [27].
  • Since B lymphoma cells themselves also express high levels of alpha 2-6-linked sialic acids, their CD22 molecules might be rendered nonfunctional by endogenous ligands [28].
  • On the other hand, VIP binding inhibition persisted even after neuraminidase treatment, suggesting that sialic acids were not directly involved [29].
  • Therefore, the single enzyme, ST8Sia II, directly transferred all alpha2,8-sialic acid residues on the alpha2,3-linked sialic acids of N-glycans of specific NCAM isoforms to yield PSA-NCAM [30].
  • The O-acetylation of mucin-bound sialyl-Le(x) gradually decreased from N to M. HPLC analysis showed that in N about 70%, in T 45% and in M only 20% of mucin-bound sialic acids are O-acetylated [31].

Analytical, diagnostic and therapeutic context of sialic acid

  • Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides) [3].
  • A similar size reduction and change in pl were observed after treatment of Pltgp40 with O-glycanase showing that sialic acids are present on O-linked oligosaccharides [32].
  • In 24 cases, the relative percentages of biosynthetically labeled non-, mono-, di-, and tri-O-acetylated sialic acids were measured after hydrolytic release, separation, and identification by paper chromatography [33].
  • Cells were recultured at 37 degrees C over time and monitored for the resialylation of the cell surface using a sensitive high pressure liquid chromatography adaptation of the thiobarbituric acid assay for sialic acids [34].
  • Sialic acids have been purified from murine erythrocyte ghosts and the existence of O-acetylated sialic acids has been confirmed: 1) by assaying with the Warren procedure before and after de-O-acetylation with 0.1 N NaOH for 45 min at 4 degrees C; 2) by thin layer chromatography on cellulose; and 3) by gas-liquid chromatography [35].


  1. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Weis, W., Brown, J.H., Cusack, S., Paulson, J.C., Skehel, J.J., Wiley, D.C. Nature (1988) [Pubmed]
  2. Diversity of microbial sialic acid metabolism. Vimr, E.R., Kalivoda, K.A., Deszo, E.L., Steenbergen, S.M. Microbiol. Mol. Biol. Rev. (2004) [Pubmed]
  3. 9-O-Acetylation of sialomucins: a novel marker of murine CD4 T cells that is regulated during maturation and activation. Krishna, M., Varki, A. J. Exp. Med. (1997) [Pubmed]
  4. Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production. Soong, G., Muir, A., Gomez, M.I., Waks, J., Reddy, B., Planet, P., Singh, P.K., Kanetko, Y., Wolfgang, M.C., Hsiao, Y.S., Tong, L., Prince, A. J. Clin. Invest. (2006) [Pubmed]
  5. GMP-140 binds to a glycoprotein receptor on human neutrophils: evidence for a lectin-like interaction. Moore, K.L., Varki, A., McEver, R.P. J. Cell Biol. (1991) [Pubmed]
  6. Distribution of sialic acids on the red blood cell membrane in beta thalassaemia. Kahane, I., Polliack, A., Rachmilewitz, E.A., Bayer, E.A., Skutelsky, E. Nature (1978) [Pubmed]
  7. Selective inactivation of influenza C esterase: a probe for detecting 9-O-acetylated sialic acids. Muchmore, E.A., Varki, A. Science (1987) [Pubmed]
  8. Alpha2,6-sialylation of cell-surface N-glycans inhibits glioma formation in vivo. Yamamoto, H., Oviedo, A., Sweeley, C., Saito, T., Moskal, J.R. Cancer Res. (2001) [Pubmed]
  9. Human influenza A virus hemagglutinin distinguishes sialyloligosaccharides in membrane-associated gangliosides as its receptor which mediates the adsorption and fusion processes of virus infection. Specificity for oligosaccharides and sialic acids and the sequence to which sialic acid is attached. Suzuki, Y., Nagao, Y., Kato, H., Matsumoto, M., Nerome, K., Nakajima, K., Nobusawa, E. J. Biol. Chem. (1986) [Pubmed]
  10. Sialic acid 9-O-acetylation on murine erythroleukemia cells affects complement activation, binding to I-type lectins, and tissue homing. Shi, W.X., Chammas, R., Varki, N.M., Powell, L., Varki, A. J. Biol. Chem. (1996) [Pubmed]
  11. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. Stevens, J., Blixt, O., Glaser, L., Taubenberger, J.K., Palese, P., Paulson, J.C., Wilson, I.A. J. Mol. Biol. (2006) [Pubmed]
  12. Sialic Acid on herpes simplex virus type 1 envelope glycoproteins is required for efficient infection of cells. Teuton, J.R., Brandt, C.R. J. Virol. (2007) [Pubmed]
  13. Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B cells. Nitschke, L., Floyd, H., Ferguson, D.J., Crocker, P.R. J. Exp. Med. (1999) [Pubmed]
  14. An autosomal dominant gene regulates the extent of 9-O-acetylation of murine erythrocyte sialic acids. A probable explanation for the variation in capacity to activate the human alternate complement pathway. Varki, A., Kornfeld, S. J. Exp. Med. (1980) [Pubmed]
  15. Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. Hammerschmidt, S., Hilse, R., van Putten, J.P., Gerardy-Schahn, R., Unkmeir, A., Frosch, M. EMBO J. (1996) [Pubmed]
  16. Bioprospecting in plants for engineered proteins. Joshi, L., Lopez, L.C. Curr. Opin. Plant Biol. (2005) [Pubmed]
  17. Characterization of the acid stability of glycosidically linked neuraminic acid: use in detecting de-N-acetyl-gangliosides in human melanoma. Sonnenburg, J.L., van Halbeek, H., Varki, A. J. Biol. Chem. (2002) [Pubmed]
  18. Human vascular adhesion protein 1 (VAP-1) is a unique sialoglycoprotein that mediates carbohydrate-dependent binding of lymphocytes to endothelial cells. Salmi, M., Jalkanen, S. J. Exp. Med. (1996) [Pubmed]
  19. Desialation of transferrin by rat liver endothelium. Irie, S., Kishimoto, T., Tavassoli, M. J. Clin. Invest. (1988) [Pubmed]
  20. Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids. Sjoberg, E.R., Powell, L.D., Klein, A., Varki, A. J. Cell Biol. (1994) [Pubmed]
  21. Rapid adhesion of nerve cells to muscle fibers from adult rats is mediated by a sialic acid-binding receptor. Bischoff, R. J. Cell Biol. (1986) [Pubmed]
  22. Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin. Diacovo, T.G., Roth, S.J., Morita, C.T., Rosat, J.P., Brenner, M.B., Springer, T.A. J. Exp. Med. (1996) [Pubmed]
  23. Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. Campbell, B.J., Finnie, I.A., Hounsell, E.F., Rhodes, J.M. J. Clin. Invest. (1995) [Pubmed]
  24. Genetic studies of low-abundance human plasma proteins. XIII. Population genetics of C1R complement subcomponent and description of new variants. Kamboh, M.I., Lyons, L.A., Ferrell, R.E. Am. J. Hum. Genet. (1989) [Pubmed]
  25. Characterization of terminal sialic acid linkages on human thymocytes. Correlation between lectin-binding phenotype and sialyltransferase expression. Baum, L.G., Derbin, K., Perillo, N.L., Wu, T., Pang, M., Uittenbogaart, C. J. Biol. Chem. (1996) [Pubmed]
  26. Characterization of a specific ligand for P-selectin on myeloid cells. A minor glycoprotein with sialylated O-linked oligosaccharides. Norgard, K.E., Moore, K.L., Diaz, S., Stults, N.L., Ushiyama, S., McEver, R.P., Cummings, R.D., Varki, A. J. Biol. Chem. (1993) [Pubmed]
  27. Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment. Raposo, G., van Santen, H.M., Leijendekker, R., Geuze, H.J., Ploegh, H.L. J. Cell Biol. (1995) [Pubmed]
  28. CD22-mediated cell adhesion to cytokine-activated human endothelial cells. Positive and negative regulation by alpha 2-6-sialylation of cellular glycoproteins. Hanasaki, K., Varki, A., Powell, L.D. J. Biol. Chem. (1995) [Pubmed]
  29. Structural and functional analysis of the human vasoactive intestinal peptide receptor glycosylation. Alteration of receptor function by wheat germ agglutinin. Chochola, J., Fabre, C., Bellan, C., Luis, J., Bourgerie, S., Abadie, B., Champion, S., Marvaldi, J., el Battari, A. J. Biol. Chem. (1993) [Pubmed]
  30. Characterization of mouse ST8Sia II (STX) as a neural cell adhesion molecule-specific polysialic acid synthase. Requirement of core alpha1,6-linked fucose and a polypeptide chain for polysialylation. Kojima, N., Tachida, Y., Yoshida, Y., Tsuji, S. J. Biol. Chem. (1996) [Pubmed]
  31. Low O-acetylation of sialyl-Le(x) contributes to its overexpression in colon carcinoma metastases. Mann, B., Klussmann, E., Vandamme-Feldhaus, V., Iwersen, M., Hanski, M.L., Riecken, E.O., Buhr, H.J., Schauer, R., Kim, Y.S., Hanski, C. Int. J. Cancer (1997) [Pubmed]
  32. Characterization of a novel self-associating Mr 40,000 platelet glycoprotein. Hildreth, J.E., Derr, D., Azorsa, D.O. Blood (1991) [Pubmed]
  33. Distribution of mono-, di, and tri-O-acetylated sialic acids in normal and neoplastic colon. Hutchins, J.T., Reading, C.L., Giavazzi, R., Hoaglund, J., Jessup, J.M. Cancer Res. (1988) [Pubmed]
  34. Intracellular trafficking of cell surface sialoglycoconjugates. Reichner, J.S., Whiteheart, S.W., Hart, G.W. J. Biol. Chem. (1988) [Pubmed]
  35. The sialoglycoproteins of murine erythrocyte ghosts. A modified periodic acid-Schiff stain procedure staining nonsubstituted and O-acetylated sialyl residues on glycopeptides. Sarris, A.H., Palade, G.E. J. Biol. Chem. (1979) [Pubmed]
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