Extraction of distance restraints from pure shift NOE experiments

Abstract

NMR techniques incorporating pure shift methods to improve signal resolution have recently attracted much attention, owing to their potential use in studies of increasingly complex molecular systems. Extraction of frequencies from these simplified spectra enables easier structure determination, but only a few of the methods presented provide structural parameters derived from signal integral measurements. In particular, for quantification of the nuclear Overhauser effect (NOE) it is highly desirable to utilize pure shift techniques where signal overlap normally prevents accurate signal integration, to enable measurement of a larger number of interatomic distances. However, robust methods for the measurement of interatomic distances using the recently developed pure shift techniques have not been reported to date. In this work we discuss some of the factors determining the accuracy of measurements of signal integrals in interferogram-based Zangger-Sterk (ZS) pure shift NMR experiments. The ZS broadband homodecoupling technique is used in different experiments designed for quantitative NOE determination from pure shift spectra. It is shown that the techniques studied can be used for quantitative extraction of NOE-derived distance restraints, as exemplified for the test case of strychnine.

Monitoring Conformational Changes in an Enzyme Conversion Inhibitor Using Pure Shift Exchange NMR Spectroscopy

“…A chunk of data is then acquired during t 3 , which is short enough to neglect the evolution of the scalar couplings. The free induction decay recorded for each t 1 increment is reconstructed from the series of chunks (corresponding to the delay t 3 ) acquired for incremented values of t 2 , yielding a 2D dataset . The resulting F2‐PSYCHE‐EXSY experiment yields pseudo‐3D datasets, which requires a longer experimental time to record than a standard 2D map.…”

“…Recently, Thiele et al. have reported an interferogram‐based Zangger‐Sterk (ZS) pure shift NOESY experiment that allows for recording 2D NOESY spectra, the correlations of which show a singlet structure in the reconstructed “direct” spectral dimension (F2) . This simplification of the observed lineshape allows for limiting signal overlap, which contributes to increase significantly the resolution.…”

“…Recently, Thiele et al have reported an interferogram-based Zangger-Sterk (ZS) pure shift NOESY experiment that allows for recording 2D NOESY spectra, the correlations of which show a singlet structure in the reconstructed "direct" spectral dimension (F2). [24] This simplification of the observed lineshape allows for limiting signal overlap, which contributes to increase significantly the resolution. More generally, they have shown that it is possible to use interferogram-based Zangger-Sterk 1 H pure shift NMR experiments to determine NOE-based interatomic distances, with a good agreement with structural model for small organic compounds.…”

perfectBASH: Band‐selective homonuclear decoupling in peptides and peptidomimetics

“…Although the TOCSY‐ and COSY‐type experiments discussed so far can be used for signal assignment within residues, for sequential assignment of the residues in peptides without specific labelling, it is usually necessary to resort to NOESY or ROESY experiment. Apart from potentially delivering distance information, both techniques can provide the sequential assignment information via intraresidue H α ( i )–H N ( i + 1) NOE contacts.…”

Ultraclean pure shift NMR

“…3a to h; averaging the 8 spectra leads to a clean spectrum with sidebands suppressed to order 7. Since the sidebands decrease rapidly in amplitude with increasing order, 16 it is rarely necessary to go beyond N = 3. At first sight the new method would appear to be very timeconsuming, but in practice this is not the case.…”