The specific cytotoxicity of immunoconjugates containing blocked ricin is dependent on the residual binding capacity of blocked ricin: evidence that the membrane binding and A-chain translocation activities of ricin cannot be separated

Biochem Biophys Res Commun. 1992 Mar 16;183(2):758-66. doi: 10.1016/0006-291x(92)90548-y.

Abstract

Recently we have developed blocked ricin, a derivative of native ricin in which the galactose-binding sites of the B-chain are blocked by covalent modification with affinity ligands. This modification impedes the binding function of the B-chain, while sparing its ability to facilitate the entry of the toxic subunit of ricin, the A-chain, into the cytoplasm. Immunotoxins prepared with blocked ricin approach the cytotoxic potency of native ricin with antibody-dependent specificity. Here we report that the high cytotoxic potency of these immunoconjugates, which is attributed to the preserved translocation function of the ricin B-chain, is dependent on the minimal residual lectin activity of blocked ricin. Our findings support the notion that two functions of ricin, membrane binding and translocation, cannot be separated.

MeSH terms

  • Antigen-Antibody Complex / metabolism
  • Antigen-Antibody Complex / toxicity*
  • Binding Sites
  • Biological Transport / drug effects
  • Cell Line
  • Cell Membrane / metabolism
  • Galactose / metabolism
  • Humans
  • Lactose / pharmacology
  • Lectins / metabolism
  • Lymphoid Tissue
  • Ricin / immunology
  • Ricin / metabolism
  • Ricin / toxicity*
  • Swainsonine / pharmacology

Substances

  • Antigen-Antibody Complex
  • Lectins
  • Ricin
  • Lactose
  • Swainsonine
  • Galactose