Structure and conformation of the tripeptide: N-t-Boc-Prolyl-Phenylalanyl-Proline (Boc-Pro-Phe-Pro)

Abstract

The structure and conformation of the tripeptide N-t-Boc-Prolyl-Phenylalanyl-Proline (Boc-Pro-Phe-Pro) (C24H33N3O6) have been investigated with X-ray crystallographic and spectroscopic methods. Two conformations of Boc-Pro-Phe-Pro crystallized in the space groupP212121 with cell dimensionsa=11.912(1),b=14.256(1),c=30.402(3). The conformation of the backbone, the orientation of the aromatic side chain and the puckering modes for the pyrrolidine rings of these conformers differ significantly. The peptide bonds exist in the generally preferredtrans conformation being slightly non-planar. These two conformations reflectα-helix- and collagen-type prolines. The crystal structures of both the conformers are stabilized by two, although different intermolecular hydrogen bonds. An intermolecular bond between the carbonyl oxygen of the carboxy terminal (3Pro) and the amide proton (2Phe) is observed for both the conformers. The second intermolecular hydrogen bond for conformer 1 is between the hydrogen of the carboxy terminal (3Pro) and the carbonyl oxygen of the N-t-Boc protecting group in contrast to the second hydrogen bond between the carbonyl oxygen of the (2Phe) residue and the hydrogen of the carboxy terminal (3Pro) for conformer 2. NMR spectroscopic studies indicated the presence of stereo-conformations due to thecis andtrans amide bonds similar to other proline-containing peptides.