Preparation and properties of a hybrid toxin of modeccin A-chain and ricin B-chain

• Published in: Biochimica et biophysica acta Vol. 761; no. 3; pp. 296 - 302
• Main Authors: Sundan, Anders, Sandvig, Kirsten, Olsnes, Sjur
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27.12.1983; Elsevier; North-Holland
• Subjects: Ammonium Chloride - pharmacology; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Disulfides; HeLa Cells - drug effects; HeLa Cells - metabolism; Humans; Hydrogen-Ion Concentration; Lectins - toxicity; Medical sciences; Modeccin A-chain; Molecular Weight; Monensin - pharmacology; Pharmacology. Drug treatments; Plant Lectins; Protein Biosynthesis - drug effects; Protein Multimerization; Ribosome Inactivating Proteins, Type 2; Ricin - analogs & derivatives; Ricin - toxicity; Ricin B-chain; Toxin; Vero cell; Toxin; Vero cell; Ricin B-chain; Modeccin A-chain; Antineoplastic agent; Molecular hybrid; Peptide chain; Preparation; HeLa cell
• ISSN: 0304-4165; 0006-3002; 1872-8006; 1878-2434
• DOI: 10.1016/0304-4165(83)90080-6

Hybrid molecules were prepared from the A- and B-chains of the two toxic lectins ricin and modeccin by dialyzing mixtures of isolated chains to allow a disulfide bridge to be formed between them. Whereas the hybrid consisting of ricin A-chain and modeccin B-chain was non-toxic, the converse hybrid, modeccin A-chain/ricin B-chain, was even more toxic to Vero cells than were the parent toxins, native ricin and modeccin. A number of drugs (NH 4Cl, monensin, trifluoperazine, verapamil, ionophore A23187) which protect cells against modeccin, but not against ricin, protected to some extent against the toxic hybrid, but less so than against native modeccin. The possibility is discussed that the modeccin A-chain of the hybrid may enter the cytosol by two routes, one which is highly efficient and identical to that used by native modeccin and another less efficient one which cannot be used by native modeccin.