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Targeting Toxins by Conjugation to Antibodies: The Effect of the Linkage Group on Biological Activity

  • D. C. Edwards
  • W. C. J. Ross
  • A. J. Cumber
  • D. P. McIntosh
  • A. Smith
  • P. E. Thorpe
  • A. Brown
  • R. H. Williams
  • A. J. S. Davies
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 13)

Abstract

Interest is growing in the potential use of conjugates of antibodies and toxins or their A chains as therapeutic agents. So far, convincing evidence has been presented on the in vitro efficacy and selectivity of such conjugates, but less information is available on in vivo properties [1]. Amongst ways in which protein-protein conjugates can be made, the use of homobifunctional agents is well known; but a more elegant heterobifunctional agent has been described involving the use of a derivatized chlorambucil (CB). This introduces in sequential manner a linkage through an amide bond onto the first protein and a piperazine ring onto the second [2]. The bonds are not subject to reduction. In another method, N-succinimidyl-3-(2-pyridyl-dithio) propionate (SPDP) is used to introduce a disulphide bridge flanked by two amide groups [3].

Keywords

Linkage Group Amide Group Amide Bond Chain Activity Sequential Manner 
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.

References

  1. 1.
    Edwards, D.C. & Thorpe, P.E. (1981) Trends Biochem. Sci. 6, 313–316.CrossRefGoogle Scholar
  2. 2.
    Thorpe, P.E., Woss, W.C.J., Cumber, A.J., Hinson, C.A., Edwards, D.C. & Davies, A.J.S. (1978) Nature 271, 752–754.CrossRefGoogle Scholar
  3. 3.
    Carlsson, J., Drevin, H. & Axën, R. (1978) Biochem. J. 173, 723–737.Google Scholar
  4. 4.
    Edwards, D.C., Ross, W.C.J., Cumber, A.J., Mcintosh, D., Smith, A., Thorpe, P.E., Brown, A., Williams, R.H. & Davies, A.J.S. (1982) Biochim. Biophys. Acta 717, 272–277.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • D. C. Edwards
    • 1
  • W. C. J. Ross
    • 1
  • A. J. Cumber
    • 1
  • D. P. McIntosh
    • 1
  • A. Smith
    • 1
  • P. E. Thorpe
    • 1
  • A. Brown
    • 1
  • R. H. Williams
    • 1
  • A. J. S. Davies
    • 1
  1. 1.Institute of Cancer ResearchRoyal Cancer HospitalLondonUK

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