Helix–coil stability constants for amino acids in nonaqueous solvents. Studies of random poly(γ‐benzyl‐L‐glutamate‐co‐L‐alanine) and poly(γ‐benzyl‐L‐glutamate‐co‐L‐leucine) in a mixed solvent

Abstract The host–guest technique has been applied to the determination of the helix–coil stability constants of two naturally occurring amino acids, L ‐alanine and L ‐leucine, in a nonaqueous solvent system. Random copolymers containing L ‐alanine and L ‐leucine, respectively, as guest residues and γ‐benzyl‐ L ‐glutamate as the host residue were synthesized. The polymers were fractionated and characterized for their amino acid content, molecular weight, and helix–coil transition behavior in a dichloroacetic acid (DCA)–1,2‐dichloroethane (DCE) mixture. Two types of helix–coil transitions were carried out on the copolymers: solvent‐induced transitions in DCA–DCE mixtures at 25°C and thermally induced transitions in a 82:18 (wt %) DCA–DCE mixture. The thermally induced transitions were analyzed by statistical mechanical methods to determine the Zimm‐Bragg parameters, σ and s , of the guest residues. The experimental data indicate that, in the nonaqueous solvent, the L ‐alanine residue stabilizes the α‐helical conformation more than the L ‐leucine residue does. This is in contrast to their behavior in aqueous solution, where the reverse is true. The implications of this finding for the analysis of helical structures in globular proteins are discussed.