Letter | Published:

Control of protein–ligand recognition using a stimuli-responsive polymer

Nature volume 378, pages 472474 (30 November 1995) | Download Citation

Subjects

Abstract

STIMULI-responsive polymers exhibit reversible phase changes in response to changes in environmental factors such as pH or temperature1–14. Conjugating such polymers to antibodies and proteins provides molecular systems for applications such as affinity separations, immunoassays and enzyme recovery and recycling15– 25. Here we show that conjugating a temperaturesensitive polymer to a genetically engineered site on a protein allows the protein's ligand binding affinity to be controlled. We synthesized a mutant of the protein streptavidin to enable sitespecific conjugation of the responsive polymer near the protein's binding site. Normal binding of biotin to the modified protein occurs below 32 °C, whereas above this temperature the polymer collapses and blocks binding. The collapse of the polymer and thus the enabling and disabling of binding, is reversible. Such environmentally triggered control of binding may find many applications in biotechnology and biomedicine, such as the control of enzyme reaction rates and of biosensor activity, and the controlled release of drugs.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Artif. Organs 19, 458–467 (1995).

  2. 2.

    & J. Macromol. Sci. Chem. A2(8), 1441–1455 (1968).

  3. 3.

    Scient. Am. 244, 124–138 (1981).

  4. 4.

    , & Am. Inst. Chem. Eng. J. 30, 578–582 (1984).

  5. 5.

    , , & Polymer J. 16, 625–631 (1984).

  6. 6.

    J. contr. Rel. 6, 297–305 (1987).

  7. 7.

    & J. contr. Rel. 8, 267–274 (1989).

  8. 8.

    Adv. Polym. Sci. 94, 28–67 (1990).

  9. 9.

    & Polymer Commun. 32, 322–323 (1991).

  10. 10.

    , & Nature 354, 291–293 (1991).

  11. 11.

    , & J. Biomater. Sci. Polym. Ed. 6, 35–40 (1994).

  12. 12.

    & J. Biomater. Sci. Polym. Ed. 5, 485–496 (1994).

  13. 13.

    & Nature 373, 49–52 (1995).

  14. 14.

    et al. Nature 374, 240–242 (1995).

  15. 15.

    & Appl. Biochem. Biotech. 14, 107–120 (1987).

  16. 16.

    & Biomaterials 11, 625–630, 631–634 (1990).

  17. 17.

    et al. Biochem. Biophys. Res. Commun. 172, 652–660 (1990).

  18. 18.

    , , & J. Polymer Sci. A28, 219–226 (1990).

  19. 19.

    & ACS Polym. Preprints 33, 468–469 (1992).

  20. 20.

    & Bioconj. Chem. 4, 509–514 (1993).

  21. 21.

    et al. Bioconj. Chem. 4, 42–46 (1993).

  22. 22.

    , & J. Biomater. Sci. Polym. Ed. 5, 407–420 (1994).

  23. 23.

    & J. Biomater. Sci. Polym. Ed. 5, 371–382 (1994).

  24. 24.

    & Macromolec. Chem. Phys. 196, 1251–1259 (1995).

  25. 25.

    , , & Bioconj. Chem. 5, 504–507 (1994).

  26. 26.

    , & J. biol. Chem. 267, 13544–13548 (1988).

  27. 27.

    , , & Science 243, 85–88 (1989).

  28. 28.

    , , & J. org. Chem. 56, 2648–2650 (1991).

  29. 29.

    , & Proc. natn. Acad. Sci. U.S.A. 92, 1754–1758 (1995).

  30. 30.

    J. appl. Crystallogr. 24, 946–950 (1991).

Download references

Author information

Affiliations

  1. Center for Bioengineering, Box 35-7962, University of Washington, Seattle, Washington 98195, USA

    • Patrick S. Stayton
    • , Cynthia Long
    •  & Ashutosh Chilkoti
  2. Center for Bioengineering, Box 35-2255, University of Washington, Seattle, Washington 98195, USA

    • Tsuyoshi Shimoboji
    • , Guohua Ghen
    •  & Allan S. Hoffman
  3. Department of Chemistry, University of Alabama at Huntsville, Huntsville, Alabama 35899 USA

    • J. Milton Harris
  4. Mitsubishi Chemical Corporation, Research and Development Division, Yokohama Research Center, 1000, Kamoshida-cho, Aoba-ku, Yokohama 277, Japan

    • Tsuyoshi Shimoboji

Authors

  1. Search for Patrick S. Stayton in:

  2. Search for Tsuyoshi Shimoboji in:

  3. Search for Cynthia Long in:

  4. Search for Ashutosh Chilkoti in:

  5. Search for Guohua Ghen in:

  6. Search for J. Milton Harris in:

  7. Search for Allan S. Hoffman in:

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/378472a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.