Use of Functionalized Poly(Ethylene Glycol)s for Modification of Polypeptides

  • Samuel Zalipsky
  • Chyi Lee
Part of the Topics in Applied Chemistry book series (TAPP)


The unique properties of poly(ethylene glycol) (or PEG) and its general compatibility with polypeptide materials facilitated development of a variety of different applications of this polymer.1–11 A marked proportion of these applications involve the use of covalently linked polypeptide-PEG adducts (reviewed elsewhere5–11). For example, a number of PEG-enzymes were shown to be useful as catalysts, soluble and active in organic solvents.7 Due to the affinity to the upper phase of PEG/Dextran and PEG/salt two-phase systems, PEG-modified proteins were proven useful both as diagnostic tools8 and in preparative separations of biological cells.9


Amino Acid Analysis Cyanuric Chloride Adenosine Deaminase Deficiency Acyl Azide Arginyl Residue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    I. N. Topchieva, Usp. Khim. 49, 494.Google Scholar
  2. I.
    N. Topchieva, Russ. Chem. Rev. 49, 260 (1980).CrossRefGoogle Scholar
  3. 2.
    K. C. Ingham, Methods Enzymol. 104, 351 (1984).PubMedCrossRefGoogle Scholar
  4. 3.
    H. Walter and G. Johansson, Anal. Biochem. 155, 215 (1986).PubMedCrossRefGoogle Scholar
  5. 4.
    E. Merrill and E. W. Salzman, Am. Soc. Artif. Internal Organs J. 6, 60 (1983).Google Scholar
  6. 5.
    M. Mutter and E. Bayer, in: The Peptides (E. Gross and J. Meienhofer, eds.), Vol. 2, p. 285, Academic Press, New York (1979).Google Scholar
  7. 6.
    V. N. R. Pillai and M. Mutter, Acc. Chem. Res. 14, 122 (1981).CrossRefGoogle Scholar
  8. 7.
    Y. Inada, K. Takahashi, T. Yoshimoto, A. Ajima, A. Matsushima, and Y. Saito, Trends in Biotechnol. 4, 190 (1986).CrossRefGoogle Scholar
  9. 8.
    B. Mattiason, Methods Enzymol. 92, 498 (1983).CrossRefGoogle Scholar
  10. 9.
    D. E. Brooks, K. A. Sharp, and S. J. Stocks, Makromol. Chem., Macromol. Symp. 17, 387 (1988).CrossRefGoogle Scholar
  11. 10.
    A. Abuchowski and F. F. Davis, in: Enzymes as Drugs (J. Holsenberg and J. Roberts, eds.), p. 367, Wiley, New York (1981).Google Scholar
  12. 11.
    S. Dreborg and E. B. Åkerblom, Crit. Rev. Therap. Drug Carrier Syst. 6, 315 (1990).Google Scholar
  13. 12.
    J. M. Harris, J. Macromol. Sci., Rev. Macromol. Chem. Phys. C25, 325 (1985).CrossRefGoogle Scholar
  14. 13.
    S. Zalipsky, C. Gilon, and A. Zilkha, J. Macromol. Sci. Chem. A21, 839 (1984).Google Scholar
  15. 14.
    S. Zalipsky, C. Gilon, and A. Zilkha, Eur. Polym. J. 19, 1177 (1983).CrossRefGoogle Scholar
  16. 15.
    D. A. Herold, K. Keil, and D. E. Bruns, Biochem. Pharmacol. 38, 73 (1989).PubMedCrossRefGoogle Scholar
  17. 16.
    H. F. Smyth, Jr., C. P. Carpenter, and C. S. Weil, J. Am. Pharm. Assoc. 39, 349 (1950).Google Scholar
  18. 17.
    A. J. Johnson, M. H. Karpatkin, and J. Newman, Br. J. Hematol. 21, 21 (1971).CrossRefGoogle Scholar
  19. 18.
    C. B. Shaffer and F. H. Critchfield, J. Am. Pharm. Assoc. 36, 152 (1947).Google Scholar
  20. 19.
    E. C. Dittmann, Naunyn-Schmeideberg’s Arch. Pharmacol. 276, 199 (1973).CrossRefGoogle Scholar
  21. 20.
    A. W. Richter and E. Åkerblom, Int. Arch. Allergy Appl. Immunol. 70, 124 (1983).PubMedCrossRefGoogle Scholar
  22. 21.
    F. F. Davis, T. Van Es, and N. C. Palczuk, U.S. Patent 4,179,337 (1979).Google Scholar
  23. 22.
    E Kawai, CRC Crit. Rev. Biotechnol. 6, 273 (1987).CrossRefGoogle Scholar
  24. 23.
    G. P. Royer and G. M. Ananthramaiah, J. Am. Chem. Soc. 101, 3394 (1979).CrossRefGoogle Scholar
  25. 24.
    J. D. Glass, L. Silver, J. Sondheimer, C. S. Pande, and J. Coderre, Biopolymers 18, 383 (1979).CrossRefGoogle Scholar
  26. 25.
    K. Ulbrich, J. Strohalm, and J. Kopecek, Makromol. Chem. 187, 1131 (1986).CrossRefGoogle Scholar
  27. 26.
    P. Pasta, S. Riva, and G. Carrea, FEBS Lett. 236, 329 (1988).PubMedCrossRefGoogle Scholar
  28. 27.
    A. Abuchowski, T. Van Es, N. C. Palczuk, and F. F. Davis, J. Biol. Chem. 252, 3578 (1977).PubMedGoogle Scholar
  29. 28.
    T. P. King, L. Kochoumian, and L. M. Lichtenstein, Arch. Biochem. Biophys. 178, 442 (1977)PubMedCrossRefGoogle Scholar
  30. T. P. King, L. Kochoumian, and N. Chiorazzi, J. Exp. Med. 149, 424 (1979).PubMedCrossRefGoogle Scholar
  31. 29.
    Y. Ashihara, T. Kono, S. Yamazaki, and Y. Inada, Biochem. Biophys. Res. Commun. 93, 385 (1978).CrossRefGoogle Scholar
  32. 30.
    H. F. Gaertner and A. J. Puigserver, Proteins 3, 130 (1988).PubMedCrossRefGoogle Scholar
  33. 31.
    S. G. Shafer and J. M. Harris, J. Polym. Sci., Polym. Chem. Ed. 24, 375 (1986).CrossRefGoogle Scholar
  34. 32.
    M. Z. Atassi, in: Immunochemistry of Proteins (M. Z. Atassi, ed.), Vol. 1, p. 1, Plenum Press, New York (1977).CrossRefGoogle Scholar
  35. 33.
    K. J. Wieder, N. C. Palczuk, T. Van Es, and F. F. Davis, J. Biol. Chem. 254, 12579 (1979).PubMedGoogle Scholar
  36. 34.
    S. Davis, A. Abuchowski, Y. K. Park, and F. F. Davis, Clin. Exp. Immunol. 46, 649 (1981).PubMedGoogle Scholar
  37. 35.
    K. Yoshinaga and J. M. Harris, J. Bioact. Compatible Polym. 4, 17 (1989).CrossRefGoogle Scholar
  38. 36.
    A. Matsushima, H. Nishimura, Y. Ashihara, Y. Yokota, and Y. Inada, Chem. Lett., 113 (1980).Google Scholar
  39. 37.
    H. Nishimura, K. Takahashi, K. Sakurai, K. Fujinuma, Y. Imamura, M. Ooba, and Y Inada, Life Sci. 33, 1467 (1983).PubMedCrossRefGoogle Scholar
  40. 38.
    K. Takahashi, A. Ajima, T. Yoshimoto, M. Okada, A. Matsushima, Y. Tamaura, and Y. Inada, J. Org. Chem. 50, 3414 (1985).CrossRefGoogle Scholar
  41. 39.
    C. C. Jackson, J. L. Charlton, K. Kuzminski, G. M. Lang, and A. H. Sehon, Anal. Biochem. 165, 114 (1987).PubMedCrossRefGoogle Scholar
  42. 40.
    A. Yoshimoto, S. G. Chao, Y. Saito, I. Imamura, H. Wada, and Y Inada, Enzyme 36, 261 (1986).PubMedGoogle Scholar
  43. 41.
    M. Rubinstein, U.S. Patent 4,101,380 (1978).Google Scholar
  44. 42.
    M. Joppich and P. L. Luisi, Makromol. Chem. 180, 1381 (1979).CrossRefGoogle Scholar
  45. 43.
    A. Abuchowski, G. Kazo, C. R. Verhoest, T. Van Es, D. Kafkewitz, M. L. Nucci, A. T. Viau, and F. F. Davis, Cancer Biochem. Biophys. 7, 175 (1984).PubMedGoogle Scholar
  46. 44.
    M. S. Hershfield, R. H. Buckley, M. L. Greenberg, A. L. Melton, R. Schiff, C. Hatem, J. Kirtzberg, M. L. Markert, R. H. Kobayashi, A. L. Kobayashi, and A. Abuchowski, N. Engl. J. Med. 316, 589 (1987).PubMedCrossRefGoogle Scholar
  47. 45.
    K. B. Hadley and P. H. Sato, Enzyme 42, 225 (1989).PubMedGoogle Scholar
  48. 46.
    K. Iwasaki, Y Iwashita, and T. Okami, U.S. Patent 4,670,417 (1987).Google Scholar
  49. 47.
    V. N. Katre, M. J. Knauf, and W. J. Laird, Proc. Natl. Acad. Sci. U.S.A. 84, 1487 (1987).PubMedCrossRefGoogle Scholar
  50. 48.
    E. Boccu, R. Largajolli, and F. M. Veronese, Z. Naturforsch. 38c, 94 (1983).Google Scholar
  51. 49.
    D. Larwood and E. Szoka, J. Labelled Compd. Radiopharm. 21, 603 (1984).CrossRefGoogle Scholar
  52. 50.
    C. O. Beauchamp, S. L. Gonias, D. P. Menapace, and S. V. Pizzo, Anal. Biochem. 131, 25 (1983).PubMedCrossRefGoogle Scholar
  53. 51.
    L. Tondelli, M. Laus, A. S. Angeloni, and P. Ferruti, J. Controlled Release 1, 251 (1985).CrossRefGoogle Scholar
  54. 52.
    C. Beauchamp, P. E. Daddona, and D. P. Menapace, in: Adv. Exp. Med. Biol. (C.H.M.M. DeDruyn, H. A. Simmons, and M. Muller, eds.), 165A, 47 (1984).Google Scholar
  55. 53.
    H. Berger and S. V. Pizzo, Blood 71, 1641 (1988).PubMedGoogle Scholar
  56. 54.
    F. M. Veronese, R. Largajolli, E. Boccu, C. A. Benassi, and O. Schiavon, Appl. Biochem. Biotechnol. 11, 141 (1985).PubMedCrossRefGoogle Scholar
  57. 55.
    S. Zalipsky, Patent pending; S. Zalipsky, R. Seltzer, and S. Meron-Rudolph, Biotechnol. Appl. Biochem. 15, 100 (1992).PubMedCrossRefGoogle Scholar
  58. 56.
    S. Zalipsky, R. Seltzer, and K. Nho, Polym. Prepr., Am. Chem. Soc, Div. Polym. Chem. 31(2), 173 (1990); in: Polymeric Drugs and Drug Delivery Systems (R. L. Dunn and R. M. Ottenbrite, eds.), p. 91, ACS Symposium Series 469, Washington, DC (1991).Google Scholar
  59. 57.
    A. Nathan, S. Zalipsky, and J. Kohn, Polym. Prepr., Am. Chem. Soc, Div. Polym. Chem. 31(2), 213 (1990).Google Scholar
  60. 58.
    A. Buckmann, M. Morr, and G. Johansson, Makromol. Chem. 182, 1379 (1981).CrossRefGoogle Scholar
  61. 59.
    M. Leonard, J. Neel, and E. Dellacherie, Tetrahedron 40, 1581 (1984).CrossRefGoogle Scholar
  62. 60.
    S. Zalipsky and G. Barany, J. Bioact. Compat. Polym. 5, 227 (1990).CrossRefGoogle Scholar
  63. 61.
    G. Johansson, J. Chromatogr. 368, 309 (1986).CrossRefGoogle Scholar
  64. 62.
    F. M. Veronese, P. Caliceti, A. Pastorino, O. Schiavon, L. Sartore, L. Banci, and L. M. Scolaro, J. Controlled Release 10, 145 (1989).CrossRefGoogle Scholar
  65. 63.
    T. Yoshimoto, M. Nakata, S. Yamaguchi, T. Funada, Y. Saito, and Y. Inada, Biotechnol. Lett. 8, 771 (1986).CrossRefGoogle Scholar
  66. 64.
    D. E. Nitecki, L. Aldwin, and M. Moreland in: Peptide Chemistry 1987 (T. Shiba and S. Sakakibara, eds.), p. 243, Protein Res. Foundation, Osaka (1988).Google Scholar
  67. 65.
    K. Shimizu, T. Nakahara, and T. Kinoshita, U.S. Patent 4,495,285 (1985).Google Scholar
  68. K. Shimizu, T. Nakahara, T. Kinoshita, J. Takatsuka, and M. Igarashi, U.S. Patent 4,640,835 (1987).Google Scholar
  69. 66.
    A. J. Garman and S. B. Kalindjian, FEBS Lett. 223, 361 (1987).PubMedCrossRefGoogle Scholar
  70. A. J. Garman, U.S. Patent 4,935,465 (1990).Google Scholar
  71. 67.
    T. P. King and C. Weiner, Int. J. Peptide Protein Res. 16, 147 (1980).CrossRefGoogle Scholar
  72. 68.
    S. Zalipsky, F. Albericio, U. Slomczynska, and G. Barany, Int. J. Peptide Protein Res. 30, 740 (1987).CrossRefGoogle Scholar
  73. 69.
    J. M. Harris, E. C. Struck, M. G. Case, M. S. Paley, M. Yalpani, J. M. Van Alstine, and D. E. Brooks, J. Polym. Sci., Polym. Chem. Ed. 22, 341 (1984).CrossRefGoogle Scholar
  74. 70.
    K. Nilsson and K. Mosbach, Methods Enzymol. 104, 56 (1984).PubMedCrossRefGoogle Scholar
  75. 71.
    C. Delgado, J. N. Patel, G. E. Francis, and D. Fisher, Biotechnol. Appl. Biochem. 12, 119 (1990).PubMedGoogle Scholar
  76. 72.
    P. Bohlen, S. Stein, W. Dairman, and S. Udenfriend, Arch. Biochem. Biophys. 155, 213 (1973).PubMedCrossRefGoogle Scholar
  77. S. J. Stocks, A. J. M. Jones, C. W. Ramey, and D. E. Brooks, Anal. Biochem. 154, 232 (1986).PubMedCrossRefGoogle Scholar
  78. 73.
    A. S. E A. Habeeb, Anal. Biochem. 14, 328 (1966).PubMedCrossRefGoogle Scholar
  79. 74.
    N. Yamasaki, A. Matsuo, and H. Isobe, Agric. Biol. Chem. 52, 2125 (1988).CrossRefGoogle Scholar
  80. 75.
    L. Sartore, R Caliceti, O. Schiavon, P. Ferruti, E. Ranucci, and F. M. Veronese, Proc. Int. Symp. Control. Rel. Bioact. Mater. 17, 208 (1990).Google Scholar
  81. 76.
    S. Zalipsky and G. Barany, Polym. Prepr., Am. Chem. Soc, Div. Polym. Chem. 27(1), 1 (1986).Google Scholar
  82. 77.
    H. Ueno and M. Fujino, Eur. Patent Appl. 0236987 (1987).Google Scholar
  83. 78.
    C. S. Pande, M. Pelzig, and J. D. Glass, Proc. Natl. Acad. Sci. U.S.A. 77, 895 (1980).PubMedCrossRefGoogle Scholar
  84. J. D. Glass, R. Miller, and G. Wesolowski, in: Peptides Structure and Function (D. Rich, ed.), p. 209, Pierce Chemical Co., Rockford, IL (1981).Google Scholar
  85. J. D. Glass, M. Pelzig, and C. S. Pande, in: Peptides 1978 (I. Z. Siemion and G. Kupryszewski, eds.), p. 235, Wroclav University Press, Poland (1979).Google Scholar
  86. 79.
    A. Sano, H. Maeda, Y. Kai, and K. Ono, Eur. Patent Appl. 0340741 (1989).Google Scholar
  87. 80.
    R. J. Goodson and N. V. Katre, Bio/Technology 8, 343 (1990).PubMedCrossRefGoogle Scholar
  88. 81.
    S. Romani, W. Gohring, L. Moroder, and E. Wunsch, in: Chemistry of Peptides and Proteins (W. Voelter, E. Bayer, Y. A. Ovchinnikov, and E. Wunsch, eds.), Vol. 2, p. 29, Walter de Gruyter, Berlin (1984).Google Scholar
  89. 82.
    A. Pollak and G. M. Whitesides, J. Am. Chem. Soc. 98, 289 (1976).CrossRefGoogle Scholar
  90. 83.
    M. Kimura, Y. Matsumura, Y. Miyauchi, and H. Maeda, Proc. Soc. Exp. Biol. Med. 188, 364 (1988).PubMedCrossRefGoogle Scholar
  91. 84.
    M. Urrutigoity and J. Souppe, Biocatalysis 2, 145 (1989).CrossRefGoogle Scholar
  92. 85.
    M.-T. Babonneau, R. Jacquier, R. Lazaro, and P. Viallefont, Tetrahedron Lett. 30, 2787 (1989).CrossRefGoogle Scholar
  93. 86.
    K. Yoshinaga, S. G. Shafer, and J. M. Harris, J. Bioact. Compatible Polym. 2, 49 (1987).CrossRefGoogle Scholar
  94. 87.
    C. Visco, C. A. Benassi, F. M. Veronese, and P. A. Maglioli, Il Farmaco 42, 549 (1987).Google Scholar
  95. 88.
    K. V. Savoca, A. Abuchowski, T. Van Es, F. F. Davis, and N. C. Palczuk, Biochem. Biophys. Acta 578, 47 (1979).PubMedCrossRefGoogle Scholar
  96. 89.
    Y. Kamisaki, H. Wada, T. Yaguara, A. Matsushima, and Y. Inada, J. Pharmacol. Exp. Ther. 216, 410 (1981).PubMedGoogle Scholar
  97. 90.
    T. Yoshimoto, T. Mihama, K. Takahashi, Y. Saito, Y. Tamaura, and Y. Inada, Biochem. Biophys. Res. Commun. 145, 908 (1987).PubMedCrossRefGoogle Scholar
  98. 91.
    C. Pina, D. Clark, and H. Blanch, Biotechnol. Tech. 3, 333 (1989).CrossRefGoogle Scholar
  99. 92.
    A. Matsushima, M. Okada, and Y. Inada, FEBS Lett. 178, 275 (1984).PubMedCrossRefGoogle Scholar
  100. 93.
    T. Nishio, K. Takahashi, T. Tsuzuki, T. Yoshimoto, Y. Kodera, A. Matsushima, Y. Saito, and Y. Inada, J. Biotechnol. 8, 39 (1988).CrossRefGoogle Scholar
  101. 94.
    Y. Inada, H. Nishimura, K. Takahashi, T. Yoshimoto, A. R. Saha, and Y. Inada, Biochem. Biophys. Res. Commun. 122, 845 (1984).PubMedCrossRefGoogle Scholar
  102. 95.
    A. Matsushima, M. Okada, K. Takahashi, T. Yoshimoto, and Y. Inada, Biochem. Int. 11, 551 (1985).Google Scholar
  103. 96.
    Y. Kodera, K. Takahashi, H. Nishimura, A. Matsushima, Y. Saito, and Y. Inada, Biotechnol. Lett. 8, 881 (1986).CrossRefGoogle Scholar
  104. 97.
    J. S. Beckman, R. L. Minor, C. W. White, J. E. Repine, G. M. Rosen, and B. A. Freeman, J. Biol. Chem. 263, 6884 (1988).PubMedGoogle Scholar
  105. 98.
    P. S. Pyatak, A. Abuchowski, and F. F. Davis, Res. Commun. Chem. Pathol. Pharmacol. 29, 113 (1980).PubMedGoogle Scholar
  106. 99.
    P. McGoff, A. C. Baziotis, and R. Maskiewicz, Chem. Pharm. Bull. 36, 3079 (1988).PubMedCrossRefGoogle Scholar
  107. 100.
    K. Miyata, Y. Nakagawa, M. Nakamura, T. Ito, K. Sugo, T. Fujita, and K. Tomoda, Agric. Biol. Chem. 52, 1575 (1988).CrossRefGoogle Scholar
  108. 101.
    A. Abuchowski and F. F. Davis, Biochem. Biophys. Acta 578, 41 (1979).PubMedCrossRefGoogle Scholar
  109. 102.
    U. Bagert and K.-H. Rohm, Biochem. Biophys. Acta 999, 36 (1989).PubMedCrossRefGoogle Scholar
  110. 103.
    H. Neumann and A. Lustig, Eur. J. Biochem. 109, 475 (1980).PubMedCrossRefGoogle Scholar
  111. 104.
    M. Leonard and E. Dellacherie, Makromol. Chem. 189, 1809 (1988).CrossRefGoogle Scholar
  112. 105.
    S. Zalipsky, F. Albericio, and G. Barany, in: Peptides: Structure and Function (V. J. Hruby and K. H. Kopple, eds.), p. 257, Pierce Chemical Co., Rockford, IL (1985).Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Samuel Zalipsky
    • 1
  • Chyi Lee
    • 1
  1. 1.Enzon, Inc.South PlainfieldUSA

Personalised recommendations