Review Article | Published:

The Oligosaccharides of Glycoproteins: Bioprocess Factors Affecting Oligosaccharide Structure and their Effect on Glycoprotein Properties

Bio/Technologyvolume 9pages13471355 (1991) | Download Citation



In this review, we organize the recent data concerning the effects of bioprocess factors on the oligosaccharide structure of human therapeutic glycoproteins, with particular emphasis on the influence of the host cell. We also discuss the effect of oligosaccharide structure on glycoprotein properties, including antigenicity, immunogenicity and plasma clearance rate.

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  1. 1

    Rademacher, T.W., Parekh, R.B. and Dwek, R.A. 1988. Glycobiology. Ann. Rev. Biochem. 57: 785–838.

  2. 2

    Goochee, C.F. and Monica, T. 1990. Environmental effects on protein glycosylation, Bio/Technology 8: 421–427.

  3. 3

    Goochee, C.F., Gramer, M., Andersen, D., Bahr, J. and Rasmussen, J.R. 1991. The oligosaccharides of glycoproteins: factors affecting their synthesis and their influence on glycoprotein properties, p. 199–240. In: Frontiers in Bioprocessing II, S. K. Sikdar, M. Bier, and P. Todd, (Eds.). American Chemical Society, Washington, D.C.

  4. 4

    Kornfeld, R. and Kornfeld, S. 1985. Assembly of asparagine-linked oligosaccharides. Ann. Rev. Biochem. 54: 631–664.

  5. 5

    Gavel, Y. and von Heijne, G. 1990. Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering. Protein Engineering 3: 433–442.

  6. 6

    Miletich, J.P. and Broze, G.J. 1990. β Protein C is not glycosylated at asparagine 329. J. Biol. Chem. 265: 11397–11404.

  7. 7

    Kaushal, G.P., Szumilo, T. and Elbein, A.D. 1988. Structure and biosynthesis of plant N-linked glycoproteins. Biochem. of Plants 14: 421–463.

  8. 8

    Kukuruzinska, M.A., Bergh, M.L.E. and Jackson, B.J. 1987. Protein glycosylation in yeast. Ann. Rev. Biochem. 56: 915–944.

  9. 9

    Tanner, W. and Lehle, L. 1987. Protein glycosylation in yeast. Biochim. Biophys. Acta 906: 81–99.

  10. 10

    Leonard, C.K., Spellman, M.W., Riddle, L., Harris, R.J., Thomas, J.N. and Gregory, T.J. 1990. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J. Biol. Chem. 265: 10373–10382.

  11. 11

    Hitzman, R.A., Chen, C.Y., Dowbenko, D.J., Renz, M.E., Liu, C., Pai, R., Simpson, N.J., Kohr, W.J., Singh, A., Chisholm, V., Hamilton, R. and Chang, C.N. 1990. Use of heterologous and homologous signal sequences for secretion of heterologous proteins from yeast. Methods in Enzymol. 185: 421–440.

  12. 12

    Ballou, C.E. 1990. Isolation, characterization, and properties of Saccharomyces cerevisiae mnn mutants with nonconditional protein glycosylation defects. Methods in Enzymol. 185: 440–469.

  13. 13

    Kuroda, K., Geyer, H., Geyer, R., Doerfler, W. and Klenk, H.-D. 1990. The oligosaccharides of influenza virus hemagglutinin expressed in insect cells by a baculovirus vector. Virology 174: 418–429.

  14. 14

    Lin, R.K., Suggs, S., Lin, C.-H., Browne, J.K., Smalling, R., Egrie, J.C., Chen, K.K., Fox, G.M., Martin, F., Stabinsky, Z., Badrawi, S.M., Lai, P.-H. and Goldwasser, E. 1985. Cloning and expression of the human erythropoietin gene. Proc. Natl. Acad. Sci. 82: 7580–7584.

  15. 15

    Jacobs, K., Shoemaker, C., Rudersdorf, R., Neill, S.D., Kaufman, R.J., Mufson, A., Seehra, J., Jones, S.S., Hewick, R., Fritsch, E.F., Kawakita, M., Shimizu, T. and Miyake, T. 1985. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature 313: 806–810.

  16. 16

    Imai, N., Kawamura, A., Higuchi, M., Oh-eda, M., Orita, T., Kawaguchi, T. and Ochi, N. 1990. Physiochemical and biological comparison of recombinant human erythropoietin with human urinary erythropoietin. J. Biochem. 107: 352–359.

  17. 17

    Quelle, F.W., Caslake, L.F., Burkert, R.E. and Wojchowski, D.M. 1989. High-level expression and purification of a recombinant human erythropoietin produced using a baculovirus vector. Blood 74: 652–657.

  18. 18

    Steiner, H., Pohl, G., Gunne, H., Hellers, M., Elhammer, A. and Hansson, L. 1988. Human tissue-type plasminogen activator synthesized by using a baculovirus vector in insect cells compared with human plasminogen activator produced in mouse cells. Gene 73: 449–457.

  19. 19

    Itoh, K., Oshima, A., Sakuraba, H. and Suzuki, Y. 1990. Expression, glycosylation, and intracellular distribution of human β-galactosidase in recombinant baculovirus-infected Spodoptera frugiperda cells. Biochem. Biophys. Res. Comm. 167: 746–753.

  20. 20

    Smith, G.E., Summers, M.D. and Fraser, M.J. 1983. Production of human beta interferon in insect cells infected with a baculovirus expression vector. Mol. Cell. Biol. 3: 2156–2165.

  21. 21

    Davidson, D.J. and Castellino, F.J. 1991. Asparagine-linked oligosaccharide processing in Lepidopteran insect cells. Temporal dependence of the nature of the oligosaccharides assembled on asparagine-289 of recombinant human plasminogen produced in baculovirus vector-infected Spodoptera frugiperda (IPLB-SF-21AE) cells. Biochem. 30: 6167–6174.

  22. 22

    March, C.J., Mosley, B., Larsen, A., Cerretti, D.P., Braedt, G., Price, V., Gillis, S., Henney, C.S., Kronheim, S.R., Grabstein, K., Conlon, P.J., Hopp, T.P. and Cosman, D. 1985. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315: 641–647.

  23. 23

    Casagli, M.C., Borri, M.G., Bigio, M., Rossi, R., Nucci, D., Bossu, P., Boraschi, D. and Antoni, G. 1989. Different conformation of purified human recombinant interleukin 1β from Escherichia coli and Saccharomyces cerevisiae is related to different level of biological activity. Biochem. Biophys. Res. Comm. 162: 357–363.

  24. 24

    Livi, G.P., Ferrara, A., Roskin, R., Simon, P.L. and Young, P.R. 1990. Secretion of N-glycosylated human recombinant interleukin-1α in Saccharomyces cerevisiae. Gene 88: 297–301.

  25. 25

    Sadler, J.E. Biosynthesis of glycoproteins: formation of O-linked oligosaccharides, Chapter 4. In: Biology of Carbohydrates, V. 2, V. Ginsburg and P. W. Robbins (Eds.). John Wiley & Sons, NY.

  26. 26

    Carraway, K.L. and Hull, S.R. 1989. O-Glycosylation pathway of mucin-type glycoproteins. BioEssays 10: 117–121.

  27. 27

    Conradt, H.S., Geyer, R., Hoppe, J., Grotjahn, L., Plessing, A. and Mohr, H. 1985. Structures of the major carbohydrates of natural human interleukin-2. Eur. J. Biochem. 153: 255–261.

  28. 28

    Conradt, H.S., Nimtz, M., Dittmar, K.E.J., Lindenmaier, W., Hoppe, J. and Hauser, H. 1989. Expression of human interleukin-2 in recombinant baby hamster kidney, Ltk, and Chinese hamster ovary cells. J. Biol. Chem. 264: 17368–17373.

  29. 29

    Tsuda, E., Kawanishi, G., Ueda, M., Masuda, S. and Sasaki, R. 1990. The role of carbohydrate in recombinant human erythropoietin. Eur. J. Biochem. 188: 405–411.

  30. 30

    Field, M.C., Dwek, R.A., Edge, C.J. and Rademacher, T.W. 1989. O-linked oligosaccharides from human serum immunoglobulin A1. Biochem. Soc. Trans. 17: 1034–1035.

  31. 31

    Oheda, M., Hase, S., Ono, M. and Ikenaka, T. 1988. Structures of the sugar chains of recombinant human granulocyte-colony-stimulating factor produced by Chinese hamster ovary cells. J. Biochem. 103: 544–546.

  32. 32

    Marti, T., Schaller, J., Rickli, E.E., Schmid, K., Kamerling, J.P., Gerwig, G.J., van Halbeek, H. and Vliegenthart, J.F.G. 1988. The N-linked and O-linked carbohydrate chains of human, bovine and porcine plasminogen. Eur. J. Biochem. 173: 57–63.

  33. 33

    Hard, K., Bitter, W., Kamerling, J.P. and Vliegenthart, J.F.G. 1989. O-mannosylation of recombinant human insulin-like growth factor I (IGF-I) produced in Saccharomyces cerevisiae. FEBS Lett. 248: 111–114.

  34. 34

    Gellerfors, P., Axelsson, K., Helander, A., Johansson, S., Kenne, L., Lindqvist, S., Pavlu, B., Skottner, A. and Fryklund, L. 1989. Isolation and characterization of a glycosylated form of human insulin-like growth factor I produced in Saccharomyces cerevisiae. J. Biol. Chem. 264: 11444–11449.

  35. 35

    Elliott, S., Fagin, K.D., Narhi, L.O., Miller, J.A., Jones, M., Koski, R., Peters, M., Hsieh, P., Sachdev, R., Rosenfeld, R.D., Rohde, M.F. and Arakawa, T. 1990. Yeast-derived recombinant human insulin-like growth factor I: production, purification, and structural characterization. J. Protein Chemistry 9: 95–104.

  36. 36

    Thomsen, D.R., Post, L.E. and Elhammer, A.P. 1990. Structure of O-glycosidically linked oligosaccharides synthesized by the insect cell line Sf9. J. Cell. Biochem. 43: 67–79.

  37. 37

    Smith, G.E., Ju, G., Ericson, B.L., Moschera, J., Lahm, H.-W., Chizzonite, R. and Summers, M.D. 1985. Modification and secretion of human interleukin 2 produced in insect cells by a baculovirus expression system. Proc. Natl. Acad. Sci. 82: 8404–8408.

  38. 38

    Kobata, A. 1984. The carbohydrates of glycoproteins, Chapter 2. In: Biology of Carbohydrates, V. 2, V. Ginsburg and P. W. Robbins (Eds.). John Wiley & Sons, NY.

  39. 39

    Paulson, J.C. 1989. Glycoproteins: what are the sugar chains for? Trends in Biochemical Sciences 14: 272–276.

  40. 40

    Paulson, J.C. and Colley, K.J. 1989. Glycosyltransferases. J. Biol. Chem. 264: 17615–17618.

  41. 41

    Parekh, R.B., Dwek, R.A., Thomas, J.R., Opdenakker, G., Rademacher, T., Wittwer, A.J., Howard, S.C., Nelson, R., Siegel, N.R., Jennings, M.G., Harakas, N.K. and Feder, J. 1989. Cell-type-specific and site-specific N-glycosylation of type I and type II human tissue plasminogen activator. Biochem. 28: 7644–7662.

  42. 42

    Galili, U., Shohet, S.B., Kobrin, E., Stults, C.L.M. and Macher, B.A. 1988. Man, apes, and old world monkeys differ from other mammals in the expression of α-galactosyl epitopes on nucleated cells. J. Biol. Chem. 263: 17755–17762.

  43. 43

    Thall, A. and Galili, U. 1990. Distribution of Galα(1,3)Galβ(1,4)-GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay. Biochem. 29: 3959–3965.

  44. 44

    Kagawa, Y., Takasaki, S., Utsumi, J., Hosoi, K., Shimizu, H., Kochibe, N. and Kobata, A. 1988. Comparatives study of the asparagine-linked sugar chains of natural human interferon-β1 and recombinant human interferon-β1 produced by three different mammalian cells. J. Biol. Chem. 263: 17508–17515.

  45. 45

    Pfeiffer, G., Schmidt, M., Strube, K.-H. and Geyer, R. 1989. Carbohydrate structure of recombinant human uterine tissue plasminogen activator expressed in mouse epithelial cells. Eur. J. Biochem. 186: 273–286.

  46. 46

    Sasaki, H., Ochi, N., Dell, A. and Fukuda, M. 1988. Site-specific glycosylation of human recombinant erythropoietin: analysis of glycopeptides or peptides at each glycosylation site by fast atom bombardment mass spectroscopy. Biochem. 27: 8618–8626.

  47. 47

    Takeuchi, M., Takasaki, S., Miyazaki, H., Takashi, K., Hoshi, S., Kochibe, N. and Kobata, A. 1988. Comparative study of the asparagine-linked sugar chains of human erythropoietins purified from urine and the culture medium of recombinant Chinese hamster ovary cells. J. Biol. Chem. 263: 3657–3663.

  48. 48

    Spellman, M.W., Basa, L.J., Leonard, C.K., Chakel, J.A., O'Connor, J.V., Wilson, S. and van Halbeek, H. 1989. Carbohydrate structures of human tissue plasminogen activator expressed in Chinese hamster ovary cells, J. Biol. Chem. 264: 14100–14111.

  49. 49

    Tsuda, E., Goto, M., Murakami, A., Akai, K., Ueda, M., Kawanishi, G., Takahashi, N., Sasaki, R., Chiba, H., Ishihara, H., Mori, M., Tejima, S., Endo, S. and Arata, Y. 1988. Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. Biochem. 27: 5646–5654.

  50. 50

    Smith, D.F., Larsen, R.D., Mattox, S., Lowe, J.B. and Cummings, R.D. 1990. Transfer and expression of a murine UDP-Gal: β-D-Galα1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. J. Biol. Chem. 265: 6225–6234.

  51. 51

    Tollefsen, S.E. and Rosenblum, J.L. 1988. Role of terminal fucose residues in clearance of human glycosylated a-amylase. Am. J. Physiol. 255: G374–G381.

  52. 52

    Campbell, C. and Stanley, P. 1983. Regulatory mutations in CHO cells induce expression of the mouse embryonic antigen SSEA-1. Cell 35: 303–309.

  53. 53

    Lee, E.U., Roth, J. and Paulson, J.C. 1989. Alteration of terminal glycosylation sequences on N-linked oligosaccharides of Chinese hamster ovary cells by expression of β-galactoside α2,6-sialyltransferase. J. Biol. Chem. 264: 13848–13855.

  54. 54

    Potvin, B., Kumar, R., Howard, D.R. and Stanley, P. 1990. Transfection of a human a-(1,3) fucosyltransferase gene into Chinese hamster ovary cells. J. Biol. Chem. 265: 1615–1622.

  55. 55

    Kobata, A. 1988. Structures, function and transformational changes of the sugar chains of glycohormones. J. Cell. Biochem. 37: 79–90.

  56. 56

    Palcic, M.M., Ripka, J., Kaur, K.J., Shoreibah, M., Hindsgaul, O. and Pierce, M.J. 1990. Regulation of N-acetylglucosaminyltransferase V activity: kinetic comparisons of parental, rous sarcoma virus-transformed BHK, and L-phytohemagglutinin-resistant BHK cells using synthetic substrates and an inhibitory substrate analog. J. Biol. Chem. 265: 6759–6769.

  57. 57

    Carlsson, S.R., Sasaki, H. and Fukuda, M. 1986. Structural variations of O-linked oligosaccharides present in leukosialin isolated from erythroid, myeloid, and T-lymphoid cell lines. J. Biol. Chem. 261: 12787–12795.

  58. 58

    Stanley, P. 1984. Glycosylation mutants of animal cells. Ann. Rev. Genet. 18: 525–552.

  59. 59

    Stanley, P. 1987. Biochemical characterization of animal cell glycosylation mutants. Methods in Enzymol. 138: 443–458.

  60. 60

    Stanley, P. 1989. Chinese hamster ovary cell mutants with multiple glycosylation defects for production of glycoproteins with minimal carbohydrate heterogeneity. Mol. Cell. Biol. 9: 377–383.

  61. 61

    Wang, X.C., O'Hanlon, T.P. and Lau, J.T.Y. 1989. Regulation of β-galactoside α2,6-sialyltransferase gene expression by dexamethasone. J. Biol. Chem. 264: 1854–1859.

  62. 62

    Larsen, R.D., Rajan, V.P., Ruff, M.M., Kukowska-Latallo, J., Cummings, R.D. and Lowe, J.B. 1989. Isolation of a cDNA encoding a murine UDPgalactose:β-D-galactosyl-1,4-N-acetyl-D-glucosaminide α-1,3-galactosyltransferase: expression cloning by gene transfer. Proc. Natl. Acad. Sci. USA. 86: 8227–8231.

  63. 63

    Conradt, H.S., Egge, H., Peter-Katalinic, J., Reiser, W., Siklosi, T. and Schaper, K. 1987. Structure of the carbohydrate moiety of human interferon-β secreted by a recombinant Chinese hamster ovary cell line. J. Biol. Chem. 262: 14600–14605.

  64. 64

    Oh-eda, M., Hasegawa, M., Hattori, K., Kuboniwa, H., Kojima, T., Orita, T., Tomonou, K., Yamazaki, T. and Ochi, N. 1990. O-linked sugar chains of human granulocyte colony-stimulating factor protect it against polymerization and denaturation allowing it to retain its biological activity. J. Biol. Chem. 265: 11432–11435.

  65. 65

    Dordal, M.S., Wang, F.F. and Goldwasser, E. 1985. The role of carbohydrate in erythropoietin action. Endocrinology 116: 2293–2299.

  66. 66

    Takeuchi, M., Takashi, K., Hoshi, S., Shimada, M. and Kobata, A. 1990. Role of sugar chains in the in vitro biological activity of human erythropoietin produced in recombinant Chinese hamster ovary cells. J. Biol. Chem. 265: 12127–12130.

  67. 67

    Hansen, L., Blue, Y., Barone, K., Collen, D. and Larsen, G.R. 1988. Functional effects of aspargine-linked oligosaccharides on natural and variant human tissue-type plasminogen activator. J. Biol. Chem. 263: 15713–15719.

  68. 68

    Wittwer, A.J. and Howard, S.C. 1990. Glycosylation at Asn-184 inhibits the conversion of single-chain to two-chain tissue-type plasminogen activator by plasmin, Biochem. 29: 4175–4180.

  69. 69

    Feizi, T. and Childs, R.A. 1987. Carbohydrates as antigenic determinants of glycoproteins. Biochem. J. 245: 1–11.

  70. 70

    Chew, W.H. and Theus, T.L. 1967. Candida precipitins. J. Immunol. 98: 220–224.

  71. 71

    Savolainen, J., Viander, M. and Koivikko, A. 1990. IgE-, IgA-, and IgG-antibody responses to carbohydrate and protein antigens of Candida albicans in asthmatic children. Allergy 40: 54–63.

  72. 72

    Alexander, S. and Elder, J.H. 1984. Carbohydrate dramatically influences immune reactivity of antisera to viral glycoprotein antigens. Science 226: 1328–1330.

  73. 73

    Schauer, R. 1988. Sialic acids as antigenic determinants of complex carbohydrates. Adv. Exp. Med. Biol. 228: 47–72.

  74. 74

    Rebois, R.V. and Liss, M.T. 1987. Antibody binding to the β-subunit of deglycosylated chorionic gonadotropin converts the antagonist to an agonist. J. Biol. Chem. 262: 3891–3896.

  75. 75

    Hattori, M., Hachisu, T., Shimohigashi, Y. and Wakabayashi, K. 1988. Conformation of the β-subunit of deglycosylated human chorionic gonadotropin in the interaction at receptor sites. Mol. Cell. Endocrinol. 57: 17–23.

  76. 76

    Sairam, M.R., Linggen, J. and Bhargavi, G.N. 1988. Alterations in antigenic structure of gonadotropins following deglycosylation. Bio-science Reports 8: 271–278.

  77. 77

    Kaluza, G., Rott, R. and Schwarz, R.T. 1980. Carbohydrate-induced conformational changes of semiliki forest virus glycoproteins determine antigenicity. Virology 102: 286–299.

  78. 78

    Kaladas, P.M., Goldberg, R. and Poretz, R.D. 1983. Rabbit anticarbohydrate antibody elicited by the lymphocyte mitogenic glycoprotein from Wistaria floribunda seeds. Mol. Immunol. 20: 727–735.

  79. 79

    Zopf, D.-A., Tsai, C.M. and Ginsburg, V. 1978. Antibodies against oligosaccharides coupled to proteins: characterization of carbohydrate specificity by radioimmune assay. Arch. Biochem. Biophys. 185: 61–71.

  80. 80

    Canaud, B., Polito-Bouloux, C., Garred, L.J., Rivory, J.-P., Donnadieu, P., Taib, J., Florence, P. and Mion, C. 1990. Recombinant human erythropoietin: 18 months' experience in hemodialysis patients. Am. J. Kidney Dis. 15: 169–175.

  81. 81

    Faulds, D. and Sorkin, E.M. 1989. Epoetin (recombinant human erythropoietin): a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis. Drugs 38: 863–899.

  82. 82

    Lim, V.S., Kirchner, P.T., Fangman, J., Richmond, J. and DeGowin, R.L. 1989. The safety and the efficacy of maintenance therapy of recombinant human erythropoietin in patients with renal insufficiency. Am. J. Kidney Dis. 14: 496–506.

  83. 83

    Moore, W.V. and Leppert, P. 1980. Role of aggregated human growth hormone (hGH) in development of antibodies to hGH. J. Clin. Endocrin. Metab. 51: 691–697.

  84. 84

    Man, N.T., Cartwright, A.J., Andrews, K.M. and Morris, G.E. 1989. Treatment of human muscle creatine kinase with glutaraldehyde preferentially increases the immunogenicity of the native conformation and permits production of high-affinity monoclonal antibodies which recognize two distinct surface epitopes. J. Immunol. Methods 125: 251–259.

  85. 85

    Reichlin, M., Nisonoff, A. and Margoliash, E. 1970. Immunological activity of cytochrome c. J. Biol. Chem. 245: 947–954.

  86. 86

    Katre, N.V. 1990. Immunogenicity of recombinant IL-2 modified by covalent attachment of polyethylene glycol. J. Immunol. 144: 209–213.

  87. 87

    Thompson, J.A., Lee, D.J., Kidd, P., Rubin, E., Kaufman, J., Bonnem, E.M. and Fefer, A. 1989. Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. J. Clin. Oncol. 7: 629–637.

  88. 88

    Hawkins, M., Horning, S., Konrad, M., Anderson, S., Sielaff, K., Rosno, S., Schiesel, J., Davis, T., DeMets, D., Merigan, T. and Borden, E. 1985. Phase I evaluation of synthetic mutant of β-interferon. Cancer Res. 45: 5914–5920.

  89. 89

    Sarna, G., Pertcheck, M., Figlin, R. and Ardalan, B. 1986. Phase I study of recombinant β ser 17 interferon in the treatment of cancer. Cancer Treat. Rep. 70: 1365–1372.

  90. 90

    Konrad, M.W., Childs, A.L., Merigan, T.C. and Borden, E.C. 1987. Assessment of the antigenic response in humans to a recombinant mutant interferon beta. J. Clin. Immunol. 7: 365–375.

  91. 91

    Briggs, D.W., Fisher, J.W. and George, W.J. 1974. Hepatic clearance of intact and desialylated erythropoietin. Am. J. of Physiol. 227: 1385–1388.

  92. 92

    Fukuda, M.N., Saski, H., Lopez, L. and Fukuda, M. 1989. Survival of recombinant erythropoietin in the circulation: the role of carbohydrates. Blood 73: 84–89.

  93. 93

    Weiss, P. and Ashwell, G. 1989. The asialoglycoprotein receptor: properties and modulation by ligand. Prog. Clin. Biol. Res. 300: 169–184.

  94. 94

    Donahue, R.E., Wang, E.A., Kaufman, R.J., Foutch, L., Leary, A.C., Witek-Giannetti, J.S., Metzger, M., Hewick, R.M., Steinbrink, D.R., Shaw, G., Kamen, R. and Clark, S.C. 1986. Effects of N-linked carbohydrate on the in vivo properties of human GM-CSF. Cold Spring Harbor Symposia on Quantitative Biology 51: 685–692.

  95. 95

    Ezekowitz, R.A.B. and Stahl, P.D. 1988. The structure and function of vertebrate mannose lectin-like proteins. J. Cell. Sci. Suppl. 9: 121–133.

  96. 96

    Stahl, P.D. 1990. The macrophage mannose receptor: current status. Am. J. Respir. Cell Mol. Biol. 2: 317–318.

  97. 97

    Owensby, D.A., Sobel, B.E. and Schwartz, A.L. 1988. Receptor-mediated endocytosis of tissue-type plasminogen activator by the human hepatoma cell line Hep G2. J. Biol. Chem. 263: 10587–10594.

  98. 98

    Tanswell, P., Schluter, M. and Krause, J. 1989. Pharmacokinetics and isolated liver perfusion of carbohydrate modified recombinant tissue-plasminogen activator. Fibrinolysis 3: 79–84.

  99. 99

    Hotchkiss, A., Refino, C.J., Leonard, C.K., O'Connor, J.V., Crowley, C., McCabe, J., Tate, K., Nakamura, G., Powers, D., Levinson, A., Mohler, M. and Spellman, M.W. 1988. The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator. Thomb. Haem. 60: 255–261.

  100. 100

    Kaniwar, Y.S. 1984. Biology of disease: biophysiology of glomerular filtration and proteinuria. Lab. Invest. 51: 7–21.

  101. 101

    Gross, V., Heinrich, P.C., vom Berg, D., Steube, K., Andus, T., Tran-Thi, T.-A., Decker, K. and Gerok, W. 1988. Involvement of various organs in the initial plasma clearance of differently glycosylated rat liver secretory proteins. Eur. J. Biochem. 173: 653–659.

  102. 102

    Gross, V., Steube, K., Tran-Thi, T.-A., Gerok, W. and Heinrich, P.C. 1989. Role of N-glycosylation for the plasma clearance of rat liver secretory glycoproteins. Biochem. Soc. Trans.:17: 21–23.

  103. 103

    Schifferli, J.A., Ng, Y.C. and Peter, D.K. 1986. The role of complement and its receptor in the elimination of immune complexes. New Eng. J. Med. 315: 488–495.

  104. 104

    Anderson, C.L. 1989. Human IgG Fc receptors. Clin. Immunol. Immunopath. 53: S63–S71.

  105. 105

    Baatrup, G. 1989. Immune complex modulation by plasma proteins. With special reference to the complement system and autoimmune diseases. Danish. Med. Bull. 36: 443–463.

  106. 106

    Vallbracht, A., Treuner, J., Flehmig, B., Joesters, K.-E. and Niethammer, D. 1981. Interferon-neutralizing antibodies in a patient treated with human fibroblast interferon. Nature 289: 496–497.

  107. 107

    Quesada, J.R. and Gutterman, J.U. 1983. Clinical study of recombinant DNA-produced leukocyte interferon (clone A) in an intermittent schedule in cancer patients. J. Natl. Cancer Inst. 70: 1041–1046.

  108. 108

    Trown, P.W., Kramer, M.J., Dennin, R.A., Connell, E.V., Palleroni, A.V., Quesada, J. and Gutterman, J.U. 1983. Antibodies to human leucocyte interferons in cancer patients. Lancet, 2: 81–87.

  109. 109

    Gribben, J.G., Devereux, S., Thomas, N.S.B., Keim, M., Jones, H.M., Goldstone, A.H. and Linch, D.C. 1990. Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 335: 434–437.

  110. 110

    Bendtzen, K., Svenson, M., Jonsson, V. and Hippe, E. 1990. Auto-antibodies to cytokines—friends or foes? Immunol. Today 11: 167–169.

  111. 111

    Tanigawara, Y., Hori, R., Okumura, K., Tsuji, J.-i., Shimizu, N., Noma, S., Suzuki, J., Livingston, D.J., Richards, S.M., Keyes, L.D., Couch, R.C. and Erickson, M.K. 1990. Pharmacokinetics in chimpanzees of recombinant human tissue-type plasminogen activator produced mouse C127 and Chinese hamster ovary cells. Chem. Pharm. Bull. 38: 517–522.

  112. 112

    Rijken, D.C., Otter, M., Kuiper, J. and van Berkel, T.J.C. 1990. Receptor-mediated endocytosis of tissue-type plasminogen activator (t-PA) by liver cells. Thrombosis Res. Supplement X: 63–71.

  113. 113

    Krause, J., Seydel, W., Heinzel, G. and Tanswell, P. 1990. Different receptors mediate the hepatic catabolism of tissue-type plasminogen activator and urokinase. Biochem. J. 267: 647–652.

  114. 114

    Spik, G., Debruyne, V., Montreuil, J., van Halbeek, H. and Vliegenthart, J.F.C. 1985. Primary structure of two sialylated triantennary glycans from human serotransferrin. FEBS Lett. 183: 65–69.

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  1. Charles F. Goochee and James R. Rasmussen: Corresponding authors.


  1. Department of Chemical Engineering, Stanford University, Stanford, CA, 94305-5025

    • Charles F. Goochee
    • , Michael J. Gramer
    • , Dana C. Andersen
    •  & Jennifer B. Bahr
  2. Genzyme, 75 Kneeland St., Boston, MA, 02111

    • James R. Rasmussen


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