Resin-supported cyclic telluride as a heterogeneous promoter of disulfide formation under solid–liquid biphasic conditions

Abstract

The oxidative crosslinking of thiols via a disulfide (SS) bond is a fundamental chemical reaction in the industrial production of protein- and peptide-based formulations. In this study, we developed a new heterogeneous catalyst/mediator, polystyrene-resin-immobilized cyclic telluride [(S)-tetrahydrotellurophen-3-amine] (RSTe), which significantly promotes the oxidation of thiols to disulfides (SS formation). Under solid–liquid biphasic reaction conditions, RSTe exhibited glutathione-peroxidase-like activity in the oxidative SS formation of 15 organic solvent- and water-soluble thiols using a peroxide (H₂O₂ or ^tBuOOH) as an oxidant. Notably, all reactions were completed within 90 min, and RSTe and the peroxide could be removed by filtration and concentration, respectively, thereby affording the target disulfides in sufficient yield and purity without further purification. This reaction system could also be utilized for SS formation in cysteine-containing polypeptide chains, suggesting the potential application of RSTe in oxidative folding, which is an essential process in the production of bioactive proteins.