Understanding the Effect of Ionic Liquid on the Folding and Conformation of Small Model Peptides

Abstract

Recent studies have shown that ionic liquids exhibit unusual but useful solvating properties. With regards to proteins, ionic liquids have emerged as a popular solvent for protein storage, as ionic liquids have been shown to stabilize the folded protein conformation when present as an additive, a co-solvent, or the primary solvent. As the overall mechanism of stabilization is not yet fully understood, we have sought to study the effect of neat ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl) imide on small model peptides. Circular dichroism and fluorescence spectroscopy of these peptides in ionic liquid indicate that helical peptides are significantly stabilized, whereas beta-hairpin peptides are destabilized by the ionic liquid solvent. In order to better understand the temperature-dependent conformational dynamics of helical peptides in 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl) imide, we have also used Fluorescence Resonance Energy Transfer, to probe the end-to-end distance of a small helical peptide, AKA2, in the ionic liquid. These results show that the increase in helicity with increasing temperature occurs concomitantly with an increase in peptide length. These results suggest the formation of low-temperature aggregates which dissolve upon heating to yield a highly stable helical structure at high temperature. These results have implication for the proper usage of ionic liquids for biomolecule storage.