Determination of the amide-plane orientations in a cyclo-beta-peptide by magic-angle-spinning deuterium-correlation spectroscopy, and comparison withthe powder X-ray structure

Previously, it has been shown that the correlation of deuterium quadrupolar tensors by spin diffusion under slow magic-angle-spinning conditions can p rovide accurate measurements of their relative orientation. In the present work we apply the technique to the cyclo-beta -peptide cyclo[(S)-beta -homo alanyl-(R)-beta -homoalanyl-(S)-beta -homoalanyl-(R)-beta -homoalanyl] with its amide hydrogens labeled by deuterons. From the 2D spin-diffusion spect rum, it is possible to determine the mutual orientation of the amide deuter on quadrupolar coupling tensors. Assuming that the molecule has four-fold m olecular symmetry, the polar angles of the symmetry axis in the principal-a xis frames of the deuterium electric-field-gradient tensors are found to be theta =15.7 degrees+/-1.0 degrees or theta =164.3 degrees +/- 1.0 degrees, and phi =172 degrees +/- 10 degrees. They are used to deduce possible conf ormations of the peptide based on the result of a previous measurement that correlated the deuterium principal quadrupolar frame with a local molecula r frame. We found eight conformations that are all consistent with the NMR measurement. Three of these have acceptably small van der Waals contact ene rgies. One of the three structures agrees, within a rmsd of 6 degrees for t he backbone dihedral angles, with an X-ray conformation.