title: Conjugation of doxorubicin to monoclonal anti-carcinoembryonic antigen antibody via novel thiol-directed cross-linking reagents.
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).
authors.affiliation: School of Pharmacy, Memorial University of Newfoundland, St John's, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lau
authors.forename: G
authors.initials: G
authors.lastname: Bérubé
authors.forename: C H
authors.initials: CH
authors.lastname: Ford
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000737:chemistry* / Q000276:immunology; D003432:Cross-Linking Reagents; D004317:Doxorubicin / Q000737:chemistry* / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D013439:Sulfhydryl Reagents
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D003432:Cross-Linking Reagents; D000922:Immunotoxins; D013439:Sulfhydryl Reagents; D004317:Doxorubicin