title: Development of a novel molecular adapter for the optimization of immunotoxins.
abstract: Immunotoxins consisting of catalytic domains of natural toxins and tumor-specific ligands were modified by introducing a molecular adapter that is able to transport the toxic domain more efficiently into cells. The adapter is a three-component structure: its core is a membrane transfer sequence (MTS) flanked by two different cleavable sequences. The directed and irreversible cellular uptake of the construct is driven by either enzymatic or chemical cleavage of the two flanking sequences. In our studies, the purified A-chain of diphtheria toxin (DT) was coupled to two different MTSs via disulfide bonds. A cytotoxicity assay revealed that the constructs containing the MTSs were more potent than DT A-chain alone and that the disulfide bond was cleaved.
authors.affiliation: Institut für Klinische Chemie und Pathobiochemie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. j.keller@ukbf.fu-berlin.de
authors.forename: J
authors.initials: J
authors.lastname: Keller
authors.forename: I
authors.initials: I
authors.lastname: Heisler
authors.forename: R
authors.initials: R
authors.lastname: Tauber
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
mesh_terms: D004167:Diphtheria Toxin / Q000737:chemistry; D000922:Immunotoxins / Q000737:chemistry*; D008024:Ligands; D008567:Membranes, Artificial; D011549:Pseudomonas / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D004167:Diphtheria Toxin; D000922:Immunotoxins; D008024:Ligands; D008567:Membranes, Artificial