Application of Room‐Temperature Aprotic and Protic Ionic Liquids for Oxidative Folding of Cysteine‐Rich Peptides |
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| Authors: | Pascal Heimer Dr Alesia A Tietze Miriam Böhm Dr Ralf Giernoth Andrea Kuchenbuch Dr Annegret Stark Dr Enrico Leipold Prof Dr Stefan H Heinemann Dr Christian Kandt Prof Dr Diana Imhof |
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| Affiliation: | 1. Department of Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, Brühler Strasse 7, 53119 Bonn (Germany);2. Technische Universit?t Darmstadt, Clemens‐Sch?pf Institute of Organic and Biochemistry, Alarich‐Weiss‐Strasse 4, 64287 Darmstadt (Germany);3. Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 K?ln (Germany);4. Institute of Chemical Technology, University of Leipzig, Linnéstrasse 3‐4, 04103 Leipzig (Germany);5. Department of Biophysics, Center for Molecular Biomedicine, Friedrich Schiller University Jena and Jena University Hospital, Hans‐Kn?ll‐Strasse 2, 07745 Jena (Germany);6. Computational Structural Biology, Life Science Informatics B‐IT, LIMES Center, Mulliken Center for Theoretical Chemistry, University of Bonn, Dahlmannstrasse 2, 53113 Bonn (Germany) |
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| Abstract: | The oxidation of the conotoxin μ‐SIIIA in different ionic liquids was investigated, and the results were compared with those obtained in C2mim]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 C2mim]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 C2mim]OAc] revealed a significant loss of the effect on ion channel NaV1.4 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. |
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| Keywords: | conotoxins cysteine‐rich ionic liquids oxidative folding peptide synthesis |
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