ABSTRACT
Diphtheria toxin is produced and secreted by strains of Corynebacterium diphtheriae that are lysogenic for one of a number of toxigenic coryne-bacteriophages. The N-terminal 21,167 fragment of toxin, fragment A, is the catalytically active toxophore responsible for the adenosine diphosphorylribosylation of elongation factor 2 within the cytosol of intoxicated cells. As long as the targeted receptors were internalized by receptor-mediated en-docytosis, the diphtheria toxin-based conjugate proteins containing the fragment B hydrophobic membrane-associating domains should be biologically active. The recombinant toxin should then be internalized and intoxicate only target cells. In addition to the minimal structural features necessary for assembly of these new receptor directed toxins, it was also clear that these recombinant fusion proteins had to be expressed in Escherichia coli in a protease-resistant form.
