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  • Title: (6-Maleimidocaproyl)hydrazone of doxorubicin--a new derivative for the preparation of immunoconjugates of doxorubicin.
    Author: Willner D, Trail PA, Hofstead SJ, King HD, Lasch SJ, Braslawsky GR, Greenfield RS, Kaneko T, Firestone RA.
    Journal: Bioconjug Chem; 1993; 4(6):521-7. PubMed ID: 7508268.
    Abstract:
    The (6-maleimidocaproyl)hydrazone of doxorubicin was synthesized and conjugated to several mAbs, including chimeric BR96, via a Michael addition reaction to thiol-containing mAbs. DTT reduction of disulfides present in the mAb was a reliable and general method for generating a consistent number of reactive SH groups. The conjugates, after purification by Bio-Beads, were free of unreacted linker and/or doxorubicin. All conjugates released doxorubicin under acidic conditions that mimic the lysosomal environment, while they were relatively stable at neutral pH. BR96 conjugates showed antigen-specific cytotoxicity.
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