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Using antibodies to perturb the coordination sphere of a transition metal complex

Abstract

METAL ions in the active sites of many metalloenzymes exhibit distinctive spectral and chemical features which are different from those of small inorganic complexes1,2. These features are the result of the unusual geometric and electronic constraints that are imposed on the metal ion within the protein environment3. Much effort has been invested to try to mimic this feature of metalloenzymes in synthetic systems, but this remains a formidable task. Here we show that one of the key lessons learned from the science of catalytic antibodies—that binding energy can be converted into chemical energy4—can be exploited to 'fine-tune' the physicochemical properties of a metal complex. We show that an antibody's binding site can reversibly perturb the coordination geometry of a metal ion, and can stabilize a high-energy coordinated species5. Specifically, antibodies designed to bind the organosilicon compound 1 (Fig. 1) also bind the geometrically similar Cu(I) complex 2. However, the antibody binds a slightly compressed form of 2, which is closer in size to 1. This distortion is manifested by a spectral shift—an 'immunochromic' effect.

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References

  1. Vallee, B. L. & Williams, R. J. P. Proc. natn. Acad. Sci. U.S.A. 59, 498–505 (1968).

    ADS  CAS  Article  Google Scholar 

  2. Williams, R. J. P. Eur. J. Biochem. 234, 363–381 (1995).

    CAS  Article  Google Scholar 

  3. Solomon, E. I. & Lowery, M. D. Science 259, 1575–1581 (1993).

    ADS  CAS  Article  Google Scholar 

  4. Schultz, P. G. & Lerner, R. A. Science 269, 1835–1842 (1995).

    ADS  CAS  Article  Google Scholar 

  5. Shokat, K. M., Leumann, C. J., Sugasawara, R. & Schultz, P. G. Angew. Chem. int. Edn engl. 27, 1172–1174 (1988).

    Article  Google Scholar 

  6. Nabeshima, T., Inaba, T., Furukawa, N., Hosoya, T. & Yano, Y. Inorg. Chem. 32, 1407–1416 (1993).

    CAS  Article  Google Scholar 

  7. Kitagawa, S. & Munakata, M. Inorg. Chem. 20, 2261–2267 (1981).

    CAS  Article  Google Scholar 

  8. Kohler, G. & Milstein, C. Nature 256, 495–497 (1975).

    ADS  CAS  Article  Google Scholar 

  9. Williams, R. J. P. J. chem. Soc. 137–145 (1955).

  10. Palmer, R. A. & Piper, T. S. Inorg. Chem. 5, 864–878 (1966).

    CAS  Article  Google Scholar 

  11. Shabat, D., Itzhaky, H., Reymond, J.-L. & Keinan, E. Nature 374, 143–146 (1995).

    ADS  CAS  Article  Google Scholar 

  12. Lewis, C. T., Krämer, T., Robinson, S. & Hilvert, D. Science 253, 1019–1022 (1991).

    ADS  CAS  Article  Google Scholar 

  13. Lewis, C. T., Paneth, P., O'Leary, M. H. & Hilvert, D. J. Am. chem. Soc. 115, 1410–1413 (1993).

    CAS  Article  Google Scholar 

  14. Keinan, E. et al. Inorg. Chem. 31, 5433–5438 (1992).

    CAS  Article  Google Scholar 

  15. Zeigler, T. Can. J. Chem. 73, 743–761 (1995).

    Article  Google Scholar 

  16. Rosa, A. & Baerends, E. J. Inorg. Chem. 33, 584–595 (1994).

    CAS  Article  Google Scholar 

  17. Noodleman, L. & Baerends, E. J. J. Am. chem. Soc. 106, 2316–2327 (1984).

    CAS  Article  Google Scholar 

  18. Jones, D. H., Hinman, A. S. & Ziegler, T. Inorg. Chem. 32, 2092–2095 (1993).

    CAS  Article  Google Scholar 

  19. Steward, M. W. & Steensgaard, J. in Antibody Affinity: Thermodynamic Aspects and Biological Significance 76–77 (CRC Press, Roca Raton, Florida, 1983).

    Google Scholar 

  20. Karlin, K. D. & Yandell, J. K. Inorg. Chem. 23, 1184–1188 (1984).

    CAS  Article  Google Scholar 

  21. Hathaway, B. J. in Comprehensive Coordination Chemistry Vol. 5 (ed. Wilkinson, G.) 533–774 (Pergamon, New York, 1987).

    Google Scholar 

  22. Johnson, J. E., Beineke, T. A. & Jacobson, R. A. J. chem. Soc. (A) 1371–1374 (1971).

  23. Foley, J., Tyagi, S. & Hathaway, B. J. J. chem. Soc. Dalton Trans. 1, 1–5 (1994).

  24. Bard, A. J. (ed.) in Encyclopedia of Electrochemistry of the Elements IX A 172–211 (Dekker, New York, 1983).

  25. Vosko, S. H., Wilk, L. & Nusair, M. Can. J. Phys. 58, 1200–1211 (1980).

    ADS  CAS  Article  Google Scholar 

  26. Becke, A. D. J. chem. Phys. 84, 4524–4529 (1986).

    ADS  CAS  Article  Google Scholar 

  27. Perdew, J. P. Phys. Rev. B33, 8822–8824 (1986).

    ADS  CAS  Article  Google Scholar 

  28. te Velde, G. & Baerends, E. J. J. comput. Phys. 99, 84–98 (1992).

    ADS  CAS  Article  Google Scholar 

  29. Ziegler, T., Rauk, A. & Baerends, E. J. Theor. chim. Acta 43, 261–273 (1977).

    CAS  Article  Google Scholar 

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Ghosh, P., Shabat, D., Kumar, S. et al. Using antibodies to perturb the coordination sphere of a transition metal complex. Nature 382, 339–341 (1996). https://doi.org/10.1038/382339a0

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