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Journal for Biophysical Chemistry

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Creation of a mixed poly(ethylene glycol) tethered-chain surface for preventing the nonspecific adsorption of proteins and peptides


Using a heterotelechelic poly(ethylene glycol) (PEG) possessing a mercapto group at one end and an acetal group at the other end (acetal-PEG-SH), the authors constructed a reactive PEG tethered-chain surface on a surface plasmon sensor (SPR) gold chip for biosensing with high sensitivity. Nonspecific bovine serum albumin adsorption on the PEG tethered-chain surface was significantly influenced by the density of the PEG chain, and was almost completely suppressed by increasing the PEG density through the repetitive treatment of the chip surface with acetal-PEG-SH. The PEG density was increased even more by adding an underbrushed layer made of shorter-PEG-SH-chain molecules (2 kDa, hereafter 2k) to the surface made of longer-PEG-SH-chain molecules (5 kDa, hereafter 5k). SPR measurement then gave an estimate of the adsorption of a series of proteins with varying sizes and isoelectric points on the PEG chain surface having an underbrushed layer (PEG5k/2k surface). As compared to other SPR surfaces, viz., a commercial carboxymethyl dextran and conventional PEG5k tethered-chain surface without an underbrushed layer, the mixed PEG5k/2k surface showed almost complete inhibition of the nonspecific adsorption not only of high-molecular-weight proteins but also of low-molecular-weight peptides.


  1. 1

    Y. Mori, S. Nagaoka, H. Takiuchi, T. Kikuchi, N. Noguchi, H. Tanzawa, and Y. Noishiki, Trans. Am. Soc. Artif. Intern. Organs 28, 459 (1982).

    CAS  Google Scholar 

  2. 2

    K. Bergdtröm, E. Österberg, K. Holmberg, A. S. Hoffman, T. P. Schuman, A. Kozlowski, and J. M. Harris, J. Biomater. Sci. Polym. Ed. 6, 123 (1994).

    Article  Google Scholar 

  3. 3

    Poly(ethylene glycol) Chemistry: Biotechnical and Biomedical Applications edited by J. M. Harris (Plenum,New York, 1992).

    Google Scholar 

  4. 4

    Hydrophilic Polymers: Performance with Environmental Acceptance, edited by J. E. Glass (American Chemistry Society, Washington, DC, 1996).

    Google Scholar 

  5. 5

    Y. S. Lin, V. Hlady, and C. G. Golander, Colloids Surf., B 3, 49 1994.

  6. 6

    N. P. Huang, J. Voeroes, S. M. De Paul, M. Textor, and N. D. Spencer, Langmuir 18, 220 (2002).

    CAS  Article  Google Scholar 

  7. 7

    S. Pasche, S. M. De Paul, J. Voeroes, N. D. Spencer, and M. Textor, Langmuir 19, 9216 (2003).

    CAS  Article  Google Scholar 

  8. 8

    N. Xia, Y. Hu, D. W. Grainger, and D. G. Castner, Langmuir 18, 3255 (2002).

    CAS  Article  Google Scholar 

  9. 9

    H. Otsuka, Y. Nagasaki, and K. Kataoka, Langmuir 20, 11285 (2004).

    CAS  Article  Google Scholar 

  10. 10

    S. I. Jeon, J. H. Lee, J. D. Andrade, and P. G. de Gennes, J. Colloid Interface Sci. 142, 159 (1991).

    CAS  Article  Google Scholar 

  11. 11

    N. L. Abbott, D. Blankschtein, and T. A. Hatton, Macromolecules 25, 5192 (1992).

    CAS  Article  Google Scholar 

  12. 12

    Y. Akiyama, H. Otsuka, Y. Nagasaki, M. Kato, and K. Kataoka, Bioconjug. Chem. 11, 947 (2000).

    CAS  Article  Google Scholar 

  13. 13

    H. Otsuka, Y. Akiyama, Y. Nagasaki, and K. Kataoka, J. Am. Chem. Soc. 123, 8226 (2001).

    CAS  Article  Google Scholar 

  14. 14

    K. Uchida, H. Otsuka, M. Kaneko, K. Kataoka, and Y. Nagasaki, Anal. Chem. 77, 1075 (2005).

    CAS  Article  Google Scholar 

  15. 15

    B. Liedberg, C. Nylander, and I. Lungström, Sens. Actuators 4, 299 (1983).

    CAS  Article  Google Scholar 

  16. 16

    J. Melendez, R. Carr, D. U. Barholomew, K. Kukanskis, J. Elkind, S. Yee, C. Furlong, and R. Woodbury, Sens. Actuators, B 35, 212 (1996).

    Article  Google Scholar 

  17. 17

    R. J. Whelan, T. Wohland, L. Neumann, B. Huang, B. Kobilka, and R. N. Zare, Anal. Chem. 74, 4570 (2002).

    CAS  Article  Google Scholar 

  18. 18

    L. G. Fägerstam, Å. Frosell-Karlsson, R. Karlsson, B. Persson, and I. Rönnberg, J. Chromatogr. 597, 397 (1992).

    Article  Google Scholar 

  19. 19

    R. Cush, J. M. Cronin, W. J. Stewart, C. H. Maule, J. Molloy, and N. J. Goddard, Biosens. Bioelectron. 8, 347 (1993).

    CAS  Article  Google Scholar 

  20. 20

    M. Malmqvist and R. Karlsson, Curr. Opin. Chem. Biol. 1, 378 (1997).

    CAS  Article  Google Scholar 

  21. 21

    T. Natsume, H. Nakayama, Ö. Jansson, T. Isobe, K. Takio, and K. Mikoshiba, Anal. Chem. 72, 4193 (2000).

    CAS  Article  Google Scholar 

  22. 22

    M. J. Gómara, G. Ercilla, M. A. Alsina, and I. Haro, J. Immunol. Methods 246, 13 (2000).

    Article  Google Scholar 

  23. 23

    R. Nakamura, H. Muguruma, K. Ikebukuro, S. Sasaki, R. Nagata, I. Karube, and H. Pedersen, Anal. Chem. 69, 4649 1997.

    CAS  Article  Google Scholar 

  24. 24

    F. F. Bier, F. Kleinjung, and F. W. Scheller, Sens. Actuators, B 38, 78 (1997).

    Article  Google Scholar 

  25. 25

    C. Williams and T. A. Addona, Trends Biotechnol. 18, 45 (2000).

    CAS  Article  Google Scholar 

  26. 26

    J. M. McDonnell, Curr. Opin. Chem. Biol. 5, 572 (2001).

    CAS  Article  Google Scholar 

  27. 27

    F. Yu and W. Knoll, Anal. Chem. 76, 1971 (2004).

    CAS  Article  Google Scholar 

  28. 28

    D. J. O’Shannessy, M. Brigham-Burke, and K. Peck, Anal. Biochem. 205, 132 (1992).

    Article  Google Scholar 

  29. 29

    E. Stenberg, B. Persson, H. Roos, and C. Urbaniczky, J. Colloid Interface Sci. 143, 513 (1991). or]30 See EPAPS Document No. E-BJIOBN-2-003704 for details on using radiolabeling protein, the absolute amount of adsorbed protein on a PEG tethered chain surface was estimated. This document can be reached through a direct link in the online article’s HTML reference section or via the EPAPS homepage (

    CAS  Article  Google Scholar 

  30. 31

    W. T. E. Bosker, P. A. Iakovlev, and W. Norde, J. Colloid Interface Sci. 286, 496 (2005).

    CAS  Article  Google Scholar 

  31. 32

    T. Ishii, H. Otsuka, K. Kataoka, and Y. Nagasaki, Langmuir 20, 561 (2004).

    CAS  Article  Google Scholar 

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Correspondence to Yukio Nagasaki.

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Uchida, K., Hoshino, Y., Tamura, A. et al. Creation of a mixed poly(ethylene glycol) tethered-chain surface for preventing the nonspecific adsorption of proteins and peptides. Biointerphases 2, 126–130 (2007).

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