Polymer Supported Methionine Selenoxide as an Excellent Immobilized Oxidant for the Formation of Disulfide Bonds in Peptides

Abstract

Two PEG-based polymer supported methionine selenoxide (MeSeO) named TentaGel-MetSeO and PEG-MetSeO were synthesized and used as immobilized oxidants for the purpose of formation of disulfide bonds in peptides under aqueous conditions. Peptide disulfide bonds were successfully synthesized by use of the two immobilized oxidants. Moreover, the oxidation of the methionine residue to its sulfoxide derivate was not observed. By comparison, the yield of disulfidecontaining peptide via PEG-MetSeO oxidation is higher than that of the disulfide-containing peptide via TentaGel-MetSeO oxidation. PEG-MetSeO can be used at least 10 cycles without the significant yield decrease. The two immobilized oxidants can be separated from the reaction mixture using filtration, making the peptide synthesis more easily.

Benzeneseleninic acid used as an oxidizing and deprotecting reagent for the synthesis of multi-cyclic peptides constrained by multiple disulfide bonds and thioether bridges

“…Regioselectvie synthesis of two disulfide bonds by the use of the BSA-ODr approach Recently, methionine selenoxide (MetSeO) as an oxidation and deprotecting reagent was used to construct two disulfide bonds in peptides (named SeODR) in a one-pot manner in our laboratories. 18 Inspired by the SeODR reaction, we considered that BSA may also be used to regioselectively construct two disulfide bonds in peptides. Thus, the synthesis of two disulfide bonds in α-conotoxin SI was first investigated by reaction of linear α-conotoxin SI-1 with BSA.…”

“…It was reported that Br − was a facilitator of the SeODR approach. 18 Thus, the reaction of BSA with oxy (Acm) was also investigated in HBr solution. As expected, oxytocin was successfully generated (entries v-viii).…”

“…4 and S40 †). 18 Next, the synthesis of three disulfide bonds in conotoxin mr3e by the use of the BSA oxidation method was investigated in phosphate buffer. The results are shown in Table S5 † and Fig.…”

“…Fig.5HPLC chromatograms: (a) reduced conotoxin mr3e, (b) reduced conotoxin mr3e was aged for 3 h in pH 7.0 phosphate buffer solution, (c) reduced conotoxin mr3e reacted with BSA for 45 min in pH 7.0 phosphate buffer solution, (d) the purified conotoxin mr3e, and (e) the conotoxin mr3e generated by the use of the SeODR and TFA/DMSO method 18. Scheme 4 The proposed mechanism for the synthesis of three disulfide bonds in conotoxin mr3e.…”

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

“…However, these reagents often require long reaction times and/or an excess amount of reagent relative to those of the polypeptides. 13 Thus, the development of techniques to obtain the desired disulfide in high yield and purity remains challenging.…”