Crystal and Molecular Structure of Benzyloxycarbonyl-\alpha-Aminoisobutyryl-L-Prolyl Methylamide: The Observation of an $X_2-{Pro}_3$ Type III \beta-Turn

The crystal and molecular structure of N-benzyloxycarbonyl-\alpha-aminoisobutyryl-L-prolyl methylamide, the amino terminal dipeptide fragment of alamethicin, has been determined using direct methods. The compound crystallizes in the orthorhombic system with the space group ${P2}_12_12_1$. Cell dimensions are a = 7.705 A, b = 11.365 A, and c = 21.904 A. The structure has been refined using conventional procedures to a final R factor of 0.054. The molecular structure possesses a 4 \rightarrow 1 intramolecular N-H- - -0 hydrogen bond formed between the CO group of the urethane moiety and the NH group of the methylamide function. The peptide backbone adopts the type III \beta-turn conformation, with ${\phi}_2$ = -51.0 deg, ${\psi}_2$ = -39.7 deg, ${\phi}_3$ = -65.0 deg, ${\psi}_3$ = -25.4 deg. An unusual feature is the occurrence of the proline residue at position 3 of the \beta-turn. The observed structure supports the view that Aib residues initiate the formation of type III \beta-turn conformations. The pyrrolidine ring is puckered in $C^{\gamma}-exo$ fashion.