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 b een undertaken in order to delineate the possible role of sequence effects in stabilizing fully extended (C-5) or local helical conformations at this residue. The three peptides Boc-Val-Dpg-Val-OMe (3), Boc-Val-Val-Dpg-Val-OM e (4), Boc-Val-Val-Dpg-Val-Val-OMe (5), have been studied by H-1-nmr method s in chloroform (CDCl3) and dimethylsulfoxide (DMSO) solutions. Even ina re latively poorly solvating medium like CDCl3, all the valine NH groups appea r to be solvent-exposed, suggesting an absence of folded beta-turn conforma tions. However, in both CDCl3 and DMSO the Dpg NH groups in all the three p eptides appear to behave like apparently solvent-inaccessible groups. In fu lly extended C-5 conformations, the proximity of the NH and CO groups of Dp g may preclude effective solvation due to a combination of stereoelectronic factors. Nuclear Overhauser effects provide support for the largely extend ed backbones. The crystal structure of peptide 3 reveals an extended confor mation at Dpg (2) with phi = -176 degrees psi = 180 degrees A correlation b etween the crystallographically observed backbone conformation and solution nmr parameters in DMSO has been attempted using available data. Dpg residu es placed in poor helix stabilizing environments may be expected to favor a local C-5 conformation. (C) 2000 John Wiley & Sons, Inc.