Conformational Choice at alpha,alpha-Di-n-Propylglycine Residues: Helical or Fully Extended Structures?

The conformational analysis of peptides containing a single alpha,alpha-di-n-propylglycine (Dpg) residue incorporated into valine-rich sequences has been undertaken in order to delineate the possible role of sequence effects in stabilizing fully extended (C5) or local helical conformations at this residue. The three peptides Boc–Val–Dpg–Val–OMe (3), Boc–Val–Val–Dpg–Val–OMe (4), Boc–Val–Val–Dpg–Val–Val–OMe (5), have been studied by 1H-nmr methods in chloroform (CDCl3) and dimethylsulfoxide (DMSO) solutions. Even in a relatively poorly solvating medium like CDCl3, all the valine NH groups appear to be solvent-exposed, suggesting an absence of folded beta-turn conformations. However, in both CDCl3 and DMSO the Dpg NH groups in all the three peptides appear to behave like apparently solvent-inaccessible groups. In fully extended C5 conformations, the proximity of the NH and CO groups of Dpg may preclude effective solvation due to a combination of stereoelectronic factors. Nuclear Overhauser effects provide support for the largely extended backbones. The crystal structure of peptide 3 reveals an extended conformation at Dpg (2) with f5 2176°, c 5 180°. A correlation between the crystallographically observed backbone conformation and solution nmr parameters in DMSO has been attempted using available data. Dpg residues placed in poor helix stabilizing environments may be expected to favor a local C5 conformation.