Disuccinimidyl suberate cross-linked ricin does not inhibit cell-free protein synthesis

Ricin was reacted with disuccinimidyl suberate, to yield a molecule in which the A and B chains were covalently cross-linked through a non-reducible bond. After purification, this cross-linked ricin analog was unable to inhibit protein synthesis in a cell-free translation system from rat liver. In contrast, after modification with the cross-linking agent the isolated ricin A chain maintained its inhibitory activity. These results support the view that ricin must be cleaved into its constituent polypeptide chains to elicit its toxicity, and suggest that reduction of the disulfide bond alone is not sufficient for ribosome inactivation in vitro.