Application of Room‐Temperature Aprotic and Protic Ionic Liquids for Oxidative Folding of Cysteine‐Rich Peptides

Abstract

The oxidation of the conotoxin μ-SIIIA in different ionic liquids was investigated, and the results were compared with those obtained in [C2 mim][OAc]. Conversion of the reduced precursor into the oxidized product was observed in the protic ILs methyl- and ethylammonium formate (MAF and EAf, respectively), whereas choline dihydrogenphosphate and Ammoeng 110 failed to yield folded peptide. However, the quality and yield of the peptide obtained in MAF and EAF were lower than in the case of the product from [C2 mim][OAc]. Reaction conditions (temperature, water content) also had an impact on peptide conversion. A closer look at the activities of μ-SIIIA versions derived from an up-scaled synthesis in [C2 mim][OAc] revealed a significant loss of the effect on ion channel NaV 1.4 relative to the buffer-oxidized peptide, whereas digestion of either μ-SIIIA product by trypsin was unaffected. This was attributed to adherence of ions from the IL to the peptide, because the disulfide connectivity is basically the same for the differentially oxidized μ-SIIIA versions.

Endeavour to simplify the frustrated concept of protein-ammonium family ionic liquid interactions

“…Among the various choices of ILs, ammonium-based ILs are seen to be most encouraging and safer alternative which can be used for the growth of pharmaceutical and various medical related applications [45][46][47][48][49][50][51][52][53][54] …”

Molecular interaction of δ-conopeptide EVIA with voltage-gated Na+ channels

“…Therefore, an established protocol of partial reduction combined with carbamidomethylation was applied. [24] After sequencing of the linear, reduced peptide as control (Supporting Fig. S3A), the buffer-oxidized peptide was analyzed and the following connectivity was confirmed: C3-C21, C10-C25, C20-C29, corresponding to the suggested fold reported earlier (Supporting information, Supporting Fig.…”

Ionic Liquids Beyond Simple Solvents: Glimpses at the State of the Art in Organic Chemistry

“…Only very few biotransformations have already been successfully carried out in neat ILs; as an example, Lozano, Vaultier, and co‐workers reported a pronounced stabilization effect of the enzyme α‐chymotrypsin in transesterification reactions . Recently, in another case, Imhof and co‐workers have found that oxidative folding of certain cysteine‐rich conotoxin peptides went along successfully only in the IL [emim]OAc, although various other ILs have been tested …”

“…[49] Recently,i na nother case, Imhof and co-workersh ave found that oxidative folding of certain cysteine-rich conotoxin peptides went along successfully only in the IL [emim]OAc, although variousother ILs have been tested. [50] In summary,o ne can say that the combination of biotransformations and ionic liquidsh as great potentialf or future applications. To date, unfortunately,g eneral trends or even sensible conclusions are not yet available.…”