Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition assay. This is because the ribosome binding site of the ricin A chain (RTA) is blocked by the B subunit in ricin holotoxin. However, it is not clear why Shiga toxin 1 (Stx1) or Shiga toxin 2 (Stx2) holotoxin is not active in a ...

Whereas brefeldin A (BFA) protected a number of cell lines against the protein toxin ricin, two of the cell lines tested were not protected but rather sensitized to ricin by BFA. EM studies revealed that upon addition of BFA the Golgi stacks in cells which were protected against the toxin rapidly transformed into a characteristic tubulo-vesicular reticulum connected to the endoplasmic reticulum...

Ricin A-chain is an N-glucosidase that attacks ribosomal RNA at a highly conserved adenine residue. Our recent crystallographic studies show that not only adenine and formycin, but also pterin-based rings can bind in the active site of ricin. For a better understanding of the means by which ricin recognizes adenine rings, the geometries and interaction energies were calculated for a number of c...

Ricin toxin (RT) is derived from castor beans, produced by the plant Ricinus communis. RT and its toxic A chain (RTA) have been used therapeutically to arm ligands that target disease-causing cells. In most cases these ligands are cell-binding monoclonal antibodies (MAbs). These ligand-toxin conjugates or immunotoxins (ITs) have shown success in clinical trials [1]. Ricin is also of concern in ...

While natural intoxications with seeds of Ricinus communis (R. communis) have long been known, the toxic protein ricin contained in the seeds is of major concern since it attracts attention of those intending criminal, terroristic and military misuse. In order to harmonize detection capabilities in expert laboratories, an international proficiency test was organized that aimed at identifying go...

Synthetic biotinylated RNA substrates were cleaved by the combined actions of ricin holotoxin and a chemical agent, N,N'-dimethylethylenediamine. The annealing of the product with a ruthenylated oligodeoxynucleotide resulted in the capture of ruthenium chelate onto magnetic beads, enabling the electrochemiluminescence (ECL)-based detection of RNA N-glycosidase activities of toxins. ECL immunoas...

Recombinant ricin A chain was chemically linked to monoclonal antibodies directed toward human breast cancer cells, a human T-cell differentiation antigen, and mouse transferrin receptor. Three types of immunotoxins were prepared; in two of them the antibody was linked to recombinant ricin A chain by a disulfide bond and in the third, a nonreducible thioether bond was used. Immunotoxins contain...

T101-ricin A-chain immunotoxin is a hybrid molecule made up of the T101 monoclonal antibody bound to the A-chain of ricin. It specifically destroys cells expressing the cell surface T65 antigen. We have designed a preclinical study to evaluate its possible use for the in vitro treatment of T-cell hematological cancers prior to autologous bone marrow transplantation. The data presented here show...

A rapid and simple method for the isolation of the two chains of ricin is described. The method involves two chromatographic runs, the first on blue-Sepharose and the second on blue dextran-Sepharose. It is moreover shown that the A chain of ricin, but not the B chain, binds to poly(U)-Sepharose.

The carbohydrate present on ricin A chain causes ricin A chain immunotoxins to be cleared rapidly in animals by the reticuloendothelial system. In an effort to overcome this problem we destroyed the carbohydrate on ricin A chain by treating it with a mixture of sodium metaperiodate and sodium cyanoborohydride and then linked the "deglycosylated" A chain to monoclonal anti-Thy 1.1 antibody. The ...