A model for the structure stabilizing effects of fluoroalcobois on peptides. A new look at an old problem

Abstract

The stabilization of helical conformations in a synthetic 21 residue peptide in aqueous solution, by addition of hexatluoroacetone hydrate (HFA) as a cosolvent is demonstrated using CD and NMR methods. Helix stabilization in melittin at acidic pH is achieved at relatively low concentrations of the fluoroalcohols, 2,2,2- trifluoroethanol (TFE) or HFA. A model for structure stabilization based on the amphipathicity ofHFA is developed. The hydrophobicity of the fluorocarbon face facilitates selective solution of peptides, permitting folding in a sequestered, hydrophobic environment. The unique hydrogen bonding properties of fluoroalcohols, poor acceptors and good donors, precludes solvent invasion of peptide backbones, in contrast to water. Peptides accquire an effective 'teflon coat' in the proposed model.