Amphipathic control of the 3(10)-/alpha-helix equilibrium in synthetic peptides

A series of short, amphipathic peptides incorporating 80% C-alpha,C-alpha-d isubstituted glycines has been prepared to investigate amphipathicity as a helix-stabilizing effect. The peptides were designed to adopt 3(10)- or alp ha -helices based on amphipathic design of the primary sequence. Characteri zation by circular dichroism spectroscopy in various media (1 : 1 acetonitr ile/water; 9: 1 acetonitrile/water; 9: 1 acetonitrile/TFE; 25 mm SDS micell es in water) indicates that the peptides selectively adopt their designed c onformation in micellar environments. We speculate that steric effects from ith and ith+3 residues interactions may destabilize the 3(10)-helix in pep tides containing amino acids with large side-chains, as with 1-aminocyclohe xane-1-carboxylic acid (Ac(6)c). This problem may be overcome by alternatin g large and small amino acids in the ith and ith+3 residues, which are stag gered in the 3(10)-helix.