Helix Nucleation by the Smallest Known α‐Helix in Water

Cyclic pentapeptides (e.g. Ac-(cyclo-1,5)-[KAXAD]-NH2; X = Ala, 1; Arg, 2) in water adopt one alpha-helical turn defined by three hydrogen bonds. NMR structure analysis reveals a slight distortion from alpha-helicity at the C-terminal aspartate caused by torsional restraints imposed by the K(i)-D(i + 4) lactam bridge. To investigate this effect on helix nucleation, the more water-soluble 2 was appended to N-, C-, or both termini of a palindromic peptide ARAARAARA (