A single carboxy-terminal arginine determines the amino-terminal helix conformation of an alanine-based peptide

Arginine is a stabilizing element in both thermophilic and low molecular weight proteins. Similarly Lys⁺Arg⁺ substitutions increase the helix content of designed helical peptides. Here we explore this 'arginine effect' by examining how Lys⁺Arg⁺ substitutions influence the 3₁₀-helix-helix equilibrium in the helical peptide Ac-(AAAAK)₃A-NH₂. The unsubstituted sequence contains a significant amount of 3₁₀-helix, however, single Lys⁺Arg⁺ substitutions shift the peptide conformation toward -helix in a position-dependent fashion. The single substitution closest to the carboxy terminus induces the largest conformational change at the helix amino terminus. These findings suggest that a single strategically-placed arginine can exert long range control on helix structure.

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