Application of room-temperature aprotic and protic ionic liquids for oxidative folding of cysteine-rich peptides.
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.
['Heimer|Pascal|P|', 'Tietze|Alesia A|AA|', 'Böhm|Miriam|M|', 'Giernoth|Ralf|R|', 'Kuchenbuch|Andrea|A|', 'Stark|Annegret|A|', 'Leipold|Enrico|E|', 'Heinemann|Stefan H|SH|', 'Kandt|Christian|C|', 'Imhof|Diana|D|']
D000818:Animals D002121:Calcium Channel Blockers D020916:Conotoxins D052078:Conus Snail D003545:Cysteine D057809:HEK293 Cells D006801:Humans D052578:Ionic Liquids D056004:Molecular Dynamics Simulation D010084:Oxidation-Reduction D010455:Peptides D017510:Protein Folding D013696:Temperature
ionic liquids oxidative folding cysteine-rich conotoxins peptide synthesis