Molecular and Crystal Structures of Two Terminally Blocked Tripeptides Corresponding to the 3–5 Sequence of the Peptaibol Antibiotics Antiamoebins

The molecular and crystal structures of the terminally blocked tripeptides methyl α‐[(acetyl‐α‐aminoisobutanoyl‐α‐aminoisobutanoyl)amino]isobutanoate trihydrate [Ac‐(Aib)3‐OMe ⋅ 3 H2O, (1)] and methyl α‐[(acetyl‐α‐aminoisobutanoyl‐α‐aminoisobutanoyl)amino]‐(R)‐sec‐butanoate monohydrate [Ac‐(Aib)2‐(R)‐Iva‐OMe ⋅ H2O, (2)], representing the 3–5 sequence of the peptaibol antibiotics antiamoebins, were determined by X‐ray diffraction. While peptide 1 is folded in the common type‐III (III′) β‐bend conformation, peptide 2 forms a type‐II β‐bend, an unusual observation for an ‐Aib‐Aib‐ sequence. A conformational energy computation analysis showed that the energy of this latter structure for an isolated Ac‐(Aib)2‐(R)‐Iva‐OMe molecule is significantly higher (ΔE > 10 kcal/mol) than that of the lowest‐energy conformation.