Crystal and molecular structure of benzyloxycarbonyl-α-aminoisobutyryl-L-prolyl methylamide: the observation of an X₂-Pro₃ Type III β-Turn

Abstract

The crystal and molecular structure of N-benzyloxycarbonyl-α-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 P2₁2₁2₁. Cell dimensions are a = 7.705 Å, b = 11.365 Å, and c = 21.904 Å. The structure has been refined using conventional procedures to a final R factor of 0.054. The molecular structure possesses a 4 →1 intramolecular N-H - O 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 β-turn conformation, with φ₂ = -51.0°, ψ₂ = -39.7°, φ₃ = -65.0°, ψ₃ = -25.4°. An unusual feature is the occurrence of the proline residue at position 3 of the -turn. The observed structure supports the view that Aib residues initiate the formation of type III β-turn conformations. The pyrrolidine ring is puckered in C^Y-exo fashion.