This study addresses a void in the existing literature on the amide-15 N chemical shift anisotropy (CSA) tensor of peptides: a systematic investigation of how the tensor varies in different peptides. Amide-15 N CSA tensors for several dipeptides are obtained using quantum chemical calculations, as well as for a series of model Ala-X and X-Ala sequences in both α-helical and β-sheet conformations (where X is one of the naturally occurring amino acids). The calculated values show a significant variation in both isolated and extended peptide structures. Hydrogen bonding at both the carbonyl group and the N-H bond of the peptide plane is shown to affect the principal values of the tensor. Calculations on model peptides indicate that the amide-15 N CSA tensor is dependent on atoms located within a distance of five bonds. Consequently, the tensor of a given peptide residue is unaffected by residues other than those adjacent to it, which implies that the amide-15 N CSA tensor should be considered in the context of tripeptide sequences. This further suggests that the amide-15 N CSA tensor of the second residue of a given tripeptide sequence may be extrapolated to the same sequence in any other polypeptide or protein, given the same backbone conformation and intermolecular environment. These conclusions will facilitate future NMR structural studies of proteins.

This study reports magnitudes and the orientation of the (13)C(alpha) chemical shift anisotropy (CSA) tensors of peptides obtained using quantum chemical calculations. The dependency of the CSA tensor parameters on the energy optimization of hydrogen atom positions and hydrogen bonding effects and the use of zwitterionic peptides in the calculations are examined. Our results indicate that the energy optimization of the hydrogen atom positions in crystal structures is necessary to obtain accurate CSA tensors. The inclusion of intermolecular effects such as hydrogen bonding in the calculations provided better agreement between the calculated and experimental values; however, the use of zwitterionic peptides in calculations, with or without the inclusion of hydrogen bonding, did not improve the results. In addition, our calculated values are in good agreement with tensor values obtained from solid-state NMR experiments on glycine-containing tripeptides. In the case of peptides containing an aromatic residue, calculations on an isolated peptide yielded more accurate isotropic shift values than the calculations on extended structures of the peptide. The calculations also suggested that the presence of an aromatic ring in the extended crystal peptide structure influences the magnitude of the delta(22) which the present level of ab initio calculations are unable to reproduce.