Predicted and trifluoroethanol-induced alpha-helicity of polypeptides.

The alpha-helix stabilizing solvent 2,2,2-trifluoroethanol (TFE) is frequently used as a medium for determining the average alpha-helicity of polypeptides by CD spectroscopy. CD spectra measured in solutions containing 10, 15, 20, 50, and 90% (vol/vol) TFE are presented for 5 peptides that were selected to demonstrate possible variations in the effect of TFE concentration on the secondary structure. The analysis is extended to 6 further peptides whose CD spectra as measured in TFE are documented in the literature. The observed alpha-helicity at a high TFE concentration is compared with the alpha-helicity determined by a structure prediction method that combines conformational filtering [S. Vajda, (1993) Journal of Molecular Biology, Vol. 229, pp. 125-145], and a Monte Carlo simulation [J. Figge et al. (1993) Protein Science, Vol. 2, pp. 155-164]. For the set of 11 peptides we find a correlation of 0.84 between the predicted [theta]222 values and the corresponding values observed by CD spectroscopy in a high concentration of TFE (p < 0.01). Although we generally find a good correlation at high TFE concentration between observed and predicted alpha-helicity, there are several peptides that do not follow the predicted behavior. An analysis of the TFE titration curves in one such case revealed that TFE can induce a sharp transition from a partial beta-sheet conformation to an alpha-helical conformation as the TFE concentration is increased above a critical value.