The effects of N-ethyl-N′-methyl imidazolium chloride on the solubility, stability and aggregation of tc-rPA

Alexander Tischer, Heiko Pultke, Andrea Topf, Matthew Auton, Christian Lange, Hauke Lilie

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The ionic liquid N-ethyl-N′-methyl imidazolium chloride (EMIMCl) has been described as being very efficient in promoting refolding of the recombinant plasminogen activator rPA. Our study reveals that molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains rather than favorably interacting with the peptide backbone. This delicate balance of favorable interactions with side chains and unfavorable interactions with the peptide backbone provides a molecular explanation of how EMIMCl suppresses protein aggregation and simultaneously promotes refolding. By contrast, high concentrations of EMIMCl denature proteins because of a reduced water content and strong favorable interactions with amino acid side chains. This denatured species is not soluble and aggregates because, in contrast to the classical denaturants, guanidine hydrochloride and urea, EMIMCl does not solubilize the peptide backbone. Structured digital abstract PNP and PNP bind by molecular sieving (1, 2, 3, 4) The ionic liquid EMIMCl is efficient in promoting the refolding of rPA. Molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains, while the interaction with the peptide backbone is unfavorable. Although a refolding enhancer on one side, high concentrations of EMIMCl result in denaturation and aggregation of proteins.

Original languageEnglish (US)
Pages (from-to)1738-1749
Number of pages12
JournalFEBS Journal
Volume281
Issue number7
DOIs
StatePublished - Apr 2014

Keywords

  • CM-rPA
  • EMIMCl
  • aggregation
  • protein solubility
  • tc-rPA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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