MUSTARD GAS CROSS-LINKING OF PROTEINS THROUGH PREFERENTIAL ALKYLATIONOF CYSTEINES

Mustard gas, bis(2-chloroethyl)sulfide, treatment of proteins is shown to generate significant amounts of covalently crosslinked protein dim ers. This is due to the preferential alkylation of cysteine residues. Crosslinking does not occur in the model protein staphylococcal nuclea se, which has no cysteine residues. Treatment of cysteine-containing m utants of staphylococcal nuclease with this chemical warfare agent did result in crosslinking. However, these dimers are slowly cleaved back to monomers by an unknown mechanism. The alkylation and crosslinking of cysteine-containing proteins by mustard gas may contribute to its t oxicity.