PREDICTED AND TRIFLUOROETHANOL-INDUCED ALPHA-HELICITY OF POLYPEPTIDES

The alpha-helix stabilizing solvent 2,2,2-trifluoroethanol (TFE) is fr equently used as a medium for determining the average alpha-helicity o f polypeptides by CD spectroscopy. CD spectra measured in solutions co ntaining 10, 15, 20, 50, and 90% (vol/vol) TFE are presented for 5 pep tides that were selected to demonstrate possible variations in the eff ect of TFE concentration on the secondary structure. The analysis is e xtended to 6 further peptides whose CD spectra as measured in TFE are documented in the literature. The observed alpha-helicity at a high TF E concentration is compared with the alpha-helicity determined by a st ructure prediction method that combines conformational filtering [S. V ajda, (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 co,responding values observed by CD spectroscopy in a high concentration of TFE (p < 0.01). Although we generally find a goon correlation at high TFE conc entration between observed and predicted alpha-helicity, there are sev eral peptides that do not follow the predicted behavior. An analysis o f the TFE titration curves in one such case revealed that TFE can indu ce a sharp transition from a partial beta-sheet conformation to an alp ha-helical conformation as the TFE concentration is inn-eased above a critical value. (C) 1996 John Wiley & Sons, Inc.