2-Sulphobenzyl, a new solubilizing and reversible protecting group for cysteine in proteins. Its scope and limitations

Abstract

S-2-Sulphobenzylcysteine and S-2-(sulphomethyl)benzylcysteine are prepared by alkylation of cysteine with omega-toluenesultone and 2,3-benzo-1,4-butanesultone respectively. Owing to the presence of the sulphonic acid group, these protected cysteine derivatives are extremely water-soluble and are stable to acid hydrolysis. The groups can be removed by treatment with sodium in liquid NH3. Reduction with tributylphosphine and simultaneous alkylation of insulin with toluenesultone under mild conditions (pH 8.3, aq. 50% propanol) gives the fully S-substituted derivatives in excellent yield; they can be separated by isoelectric precipitation of the S-sulphobenzylated B-chain. Treatment of the latter with sodium in liquid NH3 led simultaneously to the removal of the protecting groups and to the well-documented cleavage at the threonine-proline bond which can be prevented by addition of sodium amide. When deprotected A-chain was recombined with B-chain, insulin was isolated in the same yield and with the same degree of biological activity as that in the control experiment.

Combining Atom Transfer Radical Polymerization and Disulfide/Thiol Redox Chemistry: A Route to Well-Defined (Bio)degradable Polymeric Materials

“…26 Moreover, Bu 3 P does not interfere with reagents typically used to bind to the formed thiol groups, which is especially important in protein analysis. It can be used, for instance, in conjunction with 1,3-propane sultone 54 or ω-toluene sultone, 55 which trap very effectively the formed thiol groups by alkylation, thus preventing backoxidation to disulfide after exposure to air.…”