Stabilizing effects of 2‐methylalanine residues on β‐turns and α‐helices

Abstract 13C‐, 1H‐nmr, CD, and x‐ray crystallography revealed β‐turns of type III for Boc‐Gly‐L‐Ala‐Aib‐OMe, Boc‐L‐Ala‐Aib‐L‐Ala‐OMe; the 310‐helix for Boc‐Aib‐L‐Ala‐Aib‐L‐Ala‐Aib‐OMe; and antiparallel arranged α‐helices for Boc‐L‐Ala‐Aib‐Ala‐Aib‐Ala‐Glu(OBzl)‐Ala‐Aib‐Ala‐Aib‐Ala‐OMe. An N‐terminal rigid α‐helical segment is found in the polypeptide antibiotics alamethicin, suzukacillin, and trichotoxin. The α‐helix dipole is essential for their voltage‐dependent pore formation in lipid bilayer membranes, which is explained by a flip‐flop gating mechanism based on dipole–dipole interactions of parallel and antiparallel arranged α‐helices within oligomeric structures.