1 Ricin: Cytotoxicity, Biosynthesis and Use in Immunoconjugates

Publisher Summary This chapter discusses the cytotoxicity, biosynthesis, and use in immunoconjugates of ricin. Several cytotoxic proteins from plants or bacteria have been utilized for immunotoxin construction. The most widely used of these toxins are ricin and abrin from the seeds of the plants Ricinus communis and Abrusprecatorius, respectively, and diphtheria toxin, the exotoxin secreted by Corynebacterium diphtheriae lysogenic for the DNA phage B tox + . The structure, synthesis, and toxicity of ricin are described in addition to its use as a component of immunotoxins. Constraints affecting the chemotherapeutic potential of ricin are also considered together with current approaches aimed at structurally modifying ricin to remove these constraints. Ricin is exclusively present in the endosperm cells of the seeds of the castor oil ( Ricinus communis ) plant. Mature seeds contain maximum ricin concentration, the toxin being actively synthesized during the later stages of seed maturation and rapidly degraded during seed germination. Ricin is a heterodimer consisting of two distinct polypeptides held together by a single disulphide bond. The structural characterization of ricin has been simplified by the ease with which the protein can be purified in large amounts. Because both ricin and Ricinus communis agglutinin (RCA) are galactose-binding lectins, they can be separated from all other proteins present in crude extracts of Ricinus communis seeds by affinity chromatography on Sepharose 4B (the Sepharose 4B matrix contains β-galactose).