A MODEL FOR THE INTERACTION OF TRIFLUOROETHANOL WITH PEPTIDES AND PROTEINS

The structural stabilizing property of 2,2,2-trifluoroethanol (TFE) in peptides has been widely demonstrated, More recently, TFE has been sh own to enhance secondary structure content in globular proteins, and t o influence quaternary interactions in protein multimers. The molecula r mechanisms by which TFE exerts its Influence on peptide and protein structures remain poorly understood. The present analysis integrates t he known physical properties of TFE with a variety of experimental obs ervations on the interaction of TFE with peptides and proteins and on the properties of fluorocarbons. Two features of TFE, namely the hydro phobicity of the trifluoromethyl group and the hydrogen bonding charac ter (strong donor and poor acceptor), emerge as the most important fac tors for rationalising the observed effects of TFE. A model is propose d for TFE interaction with peptides which involves an initial replacem ent of the hydration shell by fluoroalcohol molecules, a process drive n by apolar interactions and favourable entropy of dehydration. Subseq uent bifurcated hydrogen-bond formation with peptide carbonyl groups, which leave intramolecular interactions unaffected, promotes secondary structure formation. (C) Munksgaard 1996.