The Reaction of Mustard Gas with Proteins

Treatment of keratin intermediate filaments with sulfur mustard analogs

“…Thus, the effect of CEES and MEC on the k8/18 pair requires that amino acids in addition to cysteine be alkylated at room temperature and near physiologic pH. Although we have not identified the modified amino acids or their locations within k8/18, previous characterization of SM reactivity indicates aspartic, glutamic [23,24] or histidine [26,27] side chains are modified by CEES and MEC, producing the effects shown in figures 2 and 3. Native keratins isolated from bovine snout are undoubtedly modified at the same positions, as well as endogenous cysteines.…”

“…Reactivity toward proteins is thought to occur preferentially at cysteines [20,22], although reactivity at the alpha-amino group (ie, the amino terminus), the imino group of histidine, and carboxylic acid groups of aspartic and glutamic acid has been demonstrated [23][24][25][26][27].…”

Specific Group Reagents for Proteins.

“…Bauer and Strauss (20) demonstrated the simultaneous iodination of the imidazole and phenolic groups of globin, but in other proteins the former do not appear to react with iodine (20,148,163,200). Mustard gas and the nitrogen mustards react non-specifically with the imidazole groups of proteins (78,125,190).…”

“…At pH 5.5-6.0, mustard gas [bis(2-chloroethyl) sulfide] appears to esterify a certain proportion of the carboxyl groups of several proteins (167). The amount of mustard introduced is closely equivalent to the carboxyl groups reacted (as determined by titration) (78). Although the tyrosine Folin color is reduced (167), it appears probable that the phenolic groups are not involved, since no appreciable change in titration between pH 8.5 and 11.0 was observed (78).…”

Mustard gas crosslinking of proteins through preferential alkylation of cysteines

“…Covalent crosslinking of such regulatory proteins in the dimeric form could result in a prolonged period where some metabolic activity is turned on or off, with many possible ill effects. Somewhat confusingly, reaction of proteins with mustard has been attributed to thiol, thioether, carboxylate, imidazole, hydroxyl, and/or aminecontaining side chains (Goffart, 1947;Davis and Ross, 1947;Peters and Wakelin, 1947;Kinsey and Grant, 1946b;Herriott et al, 1946). In order to determine if protein crosslinking occurs and the site of any such reaction, we have investigated the effect of mustard treatment on the protein staphylococcal nuclease and mutants.…”