Effects of salts on the nonequivalent stability of the α-helices of isomeric block copolypeptides

The stability of the α-helices of isomeric block copolypeptides is nonequivalent, as reported previously. In order to explore the origin of the nonequivalence, the stability of α-helix of two block copolypeptides, (L -Ala)₂₀-(L -Glu)₂₀-(L -Phe) (designated as AEF) and (L -Glu)₂₀-(L -Ala)₂₀-(L -Phe) (EAF), in aqueous solution was investigated as a function of pH, temperature, and salt concentration by the measurement of the α-helical content using CD at 223 nm. The transition temperature, T_m, as a measure of the stability of the α-helix, decreased with increasing the salt concentration for EAF, while T_m increased for AEF. The results indicate that electrostatic interactions affect the nonequivalence of such helical stability. Thermodynamic quantities, ΔG, ΔH, and ΔS, of the thermal transition from random coil to α-helix were obtained by applying the curve-fitting method to the data. The major contribution to the effects of salts seems to be the entropic term, not the enthalpy term. This is unexpected, since the salt ions would weaken electrostatic interactions between ionized groups and the dipole along the helical axis, which affect the enthalpy term. In addition, the dependence of the electrostatic effect on the salt concentration is different for EAF and AEF. There fore, the nonequivalence cannot be accounted for by only the electrostatic effect, suggesting that it originates from some intrinsic property of the α-helix.