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 3(10)-helix-->alpha-helix equilibrium in the helical peptide Ac-(AAAAK)(3)A.NH2. The unsubstituted sequence contains a significant amount of 3(10).helix, however, single Lys(+)-->Arg(+) substitutions shift the peptide conformation toward a-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.