A theoretical study on the ¹H NMR chemical shift of alanine oligopeptides

Abstract

All the NH and a-CH proton chemical shifts of alanine oligopeptides (Ac-(Ala),-NHMe, where n = 1 -6 ) with extended and a-helical conformations and anti-parallel / 3 pleated-sheet structure, were calculated by taking into account the magnetic anisotropy effect due to the C=O and two kinds of C-N bond anisotropies, and the electric-field effect. The observed spectral behavior of the NH or CH protons in Ac-Ala-NHMe and Ac-(Ala)2-NHMe could be mostly predicted from the calculation, which indicates that the NH and CH chemical shifts in these oligomers are mainly determined by the intramolecular shielding effect. On the other hand, the appearance of the "doublet a-CH peak" for oligomers with chain lengths of five or more reported by Goodman et al. could not be interpreted in terms of the intramolecular shielding effect. In this case, therefore, whether the CH protons are shielded from the solvent or not, seems to be a dominant factor for the origin of the "doublet peak". The magnetic anisotropy effect of a peptide group was also examined.

The relationship between amide proton chemical shifts and secondary structure in proteins

“…Thus, the HN proton in alanine residue i is located in the shielding (upfield shift) region of the C=O bond anisotropy of the (i-3)th alanine and of the peptide C-N bond anisotropy of the (i-2)th alanine residue, and it is these upfield effects that counteract the downfield effect caused by the directly bonded carbonyl and produce the net observed upfield shift. Herranz et al (1992) used calculated data from ubiquitin to emphasize the observation that protein NH protons on top of the plane of the preceding peptide group experience large upfield shifts, which are similar to the well-known upfield aromatic ring current shift, in agreement with our previous predictions ( Asakura, 1981). The calculations reported here show that this 'out of plane' effect is largely due to bond magnetic anisotropy.…”

“…In a previous paper (Asakura, 1981), the HN chemical shifts of 16-residue alanine oligopeptides with extended, a-helical and [3-sheet structures were calculated theoretically through summation of the shielding contributions, in order to obtain insight into the contribution of peptide groups other than the nearest neighbors. For example, the upfield shift of NH protons located in the peptide plane has been predicted by such a chemical shift calculation and this was found to be very important in interpreting chemical shifts in a-helices.…”

13 C n.m.r. study of l‐alanine peptides

“…The effects of an adjacent charge in stabilizing an opposite charge of a neighboring group is evident by comparing the pKa of L-alanine with the other peptides in Table 2. Several 'H and I3C studies of diblocked peptides of L-alanine in organic solvents have shown concentration dependent chemical shifts which has been used as evidence for selfassociation of the peptides (1). We have used the 90% 13C enriched carbonyl and methyl group analogs of the peptides at low concentrations ( 5 mM) to compare their shifts with corresponding resonances in the natural abundance spectra of the parent peptides at much higher concentrations (0.5 M).…”