Conjugation of doxorubicin to monoclonal anti-carcinoembryonic antigen antibody via novel thiol-directed cross-linking reagents

Bioorg Med Chem. 1995 Oct;3(10):1299-304. doi: 10.1016/0968-0896(95)00125-z.

Abstract

In order to improve the available methods to produce an immunoconjugate the use of longer heterobifunctional cross-linking reagents were investigated. Two new maleimidobenzoyl spacers have been synthesized in a one step process from 4-maleimidobenzoic acid. The new heterobifunctional cross-linking reagents were fully characterized by their IR, 1H NMR, 13C NMR and mass spectra. These spacers are selectively attached to NH2-3' of the daunosamine moiety of doxorubicin. The spacer-doxorubicin derivatives were also characterized by 1H NMR spectrometry before coupling to thiol groups of thiolated anti-carcinoembryonic antigen (CEA) monoclonal antibody (11-285-14). These conjugates contain 1.51-3.44 molecules of drug for each molecule of monoclonal antibody (MAb).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Carcinoembryonic Antigen / chemistry*
  • Carcinoembryonic Antigen / immunology
  • Cross-Linking Reagents
  • Doxorubicin / chemistry*
  • Doxorubicin / immunology
  • Hydrogen-Ion Concentration
  • Immunotoxins / chemistry*
  • Immunotoxins / immunology
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Spectrophotometry, Infrared
  • Sulfhydryl Reagents

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Cross-Linking Reagents
  • Immunotoxins
  • Sulfhydryl Reagents
  • Doxorubicin