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Chemical Modifications of the Toxic Lectins Abrin and Ricin

1978; Wiley; Volume: 84; Issue: 2 Linguagem: Inglês

10.1111/j.1432-1033.1978.tb12171.x

1432-1033

Kirsten Sandvig, Sjur Olsnes, Alexander Pihl,

Biochemical and Structural Characterization

Abrin, ricin and their isolated A and B chains were subjected to various chemical treatments and the effect on their toxicity in mice, their ability to inhibit protein synthesis in a cell-free system and to induce indirect hemagglutination were studied. Reductive methylation reduced slightly the toxicity of abrin in mice and its ability to induce indirect agglutination, while its ability to inhibit protein synthesis in a cell-free system was unimpaired, indicating reduced ability of the B chain to bind to cell-surface receptors. The effect on ricin was slighter. Both periodate oxidation of methylated abrin and succinylation of abrin reduced strongly its toxicity to mice and its hemagglutinating ability, while its ability to inhibit protein synthesis in a cell-free system was much less reduced. Such treatments of ricin had little effect on its biological properties. Acetylation of tyrosyl groups with N-acetyl-imidazole strongly reduced the toxicity of abrin and ricin as well as their ability to induce hemagglutination. The change could be fully reversed by removing the acetyl groups introduced, indicating that tyrosyl groups are important for the binding sites of the toxin B chains. There was no change in the ability of the toxins to inhibit cell-free protein synthesis. Attempts to modify tryptophan groups in abrin and ricin by treatment with N-bromosuccinimide resulted in strongly reduced toxicity and in most cases the proteins showed changes in immunological and electrophoretic properties. In contrast, the toxins were much less affected by treatment with 2-hydroxy-5-nitrobenzyl bromide. Only when the treatment was carried out at low pH was the toxicity reduced. The results demonstrate that abrin and ricin may be chemically modified to inactivate primarily the B chain, responsible for binding of the toxins to animal cells, without affecting appreciably the activity of the A chain which is responsible for the toxic action of the proteins.