"Teflon-coated peptides": hexafluoroacetone trihydrate as a structure stabilizer for peptides

Abstract

In the last 30 years, since the early work of Goodman and co-workers introducing trifluoroethanol as a solvent in peptide conformational analysis,1,2 the ability of fluoroalcohols to stabilize secondary structures in peptides in aqueous solution is well documented.3-7 However, the detailed molecular mechanisms remain to be understood. 3,4,8-12 2,2,2-Trifluoroethanol (TFE) has been the most widely used fluoroalcohol additive to aqueous solutions of peptides and proteins.4,13-18 We describe in this communication the superior structure-stabilization properties of hexafluoroacetone trihydrate (HFA, a covalent hydrate, of the ketone, a gem diol, hexafluoropropan-2,2- diol) 19-21 and provide a rationale for the induction of intramolecularly hydrogen-bonded conformations in peptides, in aqueous fluoroalcohol solutions.