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 NaDodSO 4 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 NaDodSO 4 solution. Most striking is the difference between this polypeptide, (Lys 2 ‐Ala 2 ) n and (Lys x , Ala y ) n , even though they all have equimolar Lys and Ala. (Lys 2 ‐Ala 2 ) n was partially helical in 2.5–5 m M NaDodSO 4 but approached the unordered form in 50 m M NaDodSO 4 , whereas (Lys 50 , Ala 50 ) n was completely helical in all NaDodSO 4 concentrations. Even Lysrich (Lys 2 ‐Ala) n and (Lys 3 ‐Ala) n formed a partial helix and a trace of the β‐form, respectively, in low NaDodSO 4 concentrations; both reverted to the unordered form in high NaDodSO 4 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.