Context-dependent conformation of diethylglycine residues in peptides

Diethylglycine (Deg) residues incorporated into peptides can stabilize full y extended (C-5) or helical conformations. The conformations of three tetra peptides Boc-Xxx-Deg-Xxx-Deg-OMe (Xxx-Gly, GD4; Leu, LD4 and Pro, PD4) have been investigated by NMR. In the Gly and Leu peptides, NOE data suggest th at the local conformations at the Deg residues are fully extended. Low temp erature coefficients for the Deg(2) and Deg(4) NH groups are consistent wit h their inaccessibility to solvent, in a C-5 conformation. NMR evidence sup ports a folded beta-turn conformation involving Deg(2)-Gly(3), stabilized b y a 4 --> 1 intramolecular hydrogen bond between Pro(1) CO and Deg(4) NH in the proline containing peptide (PD4). The crystal structure of GD4 reveals a hydrated multiple turn conformation with Gly(1)-Deg(2) adopting a distor ted type II/II' conformation, while the Deg(2)-Pro(3) segment adopts a type III/III' structure. A lone water molecule is inserted into the potential 4 --> 1 hydrogen bond of the Gly(1)-Deg(2) beta-turn.