Conformation of sequential and random copolypeptides of lysine and alanine in sodium dodecyl sulfate solution

A series of sequential polypeptides, (Lys_i-Ala_j)_n, and random copolypeptides, (Lys^x, Ala^y)_n, were synthesized. The competitive effect of Ala, a helix former, and Lys, whose homopolymer has a β-form in neutral NaDodSO₄ solution, was determined by CD and absorption spectroscopy. All the polypeptides studied were unordered in neutral solution without the surfactant. Of the six sequential polypeptides only (Lys-Ala)_n adopted a stable β-form in NaDodSO₄ solution. Most striking is the difference between this polypeptide, (Lys₂-Ala₂)_n and (Lys^x, Ala^y)_n, even though they all have equimolar Lys and Ala. (Lys₂-Ala₂)_n was partially helical in 2.5–5 mM NaDodSO₄ but approached the unordered form in 50 mM NaDodSO₄, whereas (Lys⁵⁰, Ala⁵⁰)_n was completely helical in all NaDodSO₄ concentrations. Even Lysrich (Lys₂-Ala)_n and (Lys₃-Ala)_n formed a partial helix and a trace of the β-form, respectively, in low NaDodSO₄ concentrations; both reverted to the unordered form in high NaDodSO₄ concentrations. These results can be explained by Pauling-Corey's model for β-pleated sheets. Only (Lys-Ala)_n has all DodSO-bound Lys⁺ residues on one side and Ala residues on the other side of the polypeptide chain. They can nestle quiet efficiently in a β-sheet and between neighboring β-sheets. Our results further imply that random copolypeptides are not completely random; they comprise varying segments of (Lys_k-Ala_m), where k and m could vary from zero to a small integer.