Non‐uniform sampling for NOESY? A case study on spiramycin

Abstract

To date, most nuclear magnetic resonance (NMR)-based 3-D structure determinations of both small molecules and of biopolymers utilize the nuclear Overhauser effect (NOE) via NOESY spectra. The acquisition of high-quality NOESY spectra is a prerequisite for quantitative analysis providing accurate interatomic distances. As the acquisition of NOE build-ups is time-consuming, acceleration of the process by the use of non-uniform sampling (NUS) may seem beneficial; however, the quantitativity of NOESY spectra acquired with NUS has not yet been validated. Herein, NOESY spectra with various extents of NUS have been recorded, artificial NUS spectra with two different sampling schemes created, and by using two different NUS reconstruction algorithms the influence of NUS on the data quality was evaluated. Using statistical analyses, NUS is demonstrated to influence the accuracy of quantitative NOE experiments. The NOE-based distances show an increased error as the sampling density decreases. Weak NOE signals are affected more severely by NUS than more intense ones. The application of NUS with NOESY comes at two major costs: the interatomic distances are determined with lower accuracy and long-range correlations are lost.

Conformational Preferences at the Glycosidic Linkage of Saccharides in Solution as Deduced from NMR Experiments and MD Simulations: Comparison to Crystal Structures

“…This is commonly carried out by relying on the nuclear Overhauser effect (NOE) [69] by identifying the protons that show NOEs, but also by noting proton‐pairs for which the NOE is absent as this may indicate longer distances in the molecule. However, if the molecule is flexible an ensemble of conformational states has to be considered due to the motional averaging that then takes place [70,71] . For the conformational analysis of disaccharides 1 – 3 1D 1 H, 1 H‐NOESY NMR experiments were carried out using a selective excitation of the anomeric proton of the terminal sugar residue for an array of mixing times to obtain buildup curves that subsequently were analyzed according to Dixon et al [34] .…”

Enhanced Nuclear Magnetic Resonance Spectroscopy with Isotropic Mixing as a Pseudodimension

“…Yet, significant differences between the magnitudes of the diagonal and off-diagonal peaks make NOESY very challenging for NUS. 58 Moreover, the shape of the intensity build-up curves in NOESY is not as “sophisticated” as that in TOCSY and thus does not require a dense sampling. Actually, two well-placed points (mixing time values) provide sufficient information, making it possible to determine internuclear distances.…”

“…In this way, one obtains a “continuous” intensity build-up curve with a well-described linear part that can be used to calculate internuclear distances. Yet, significant differences between the magnitudes of the diagonal and off-diagonal peaks make NOESY very challenging for NUS . Moreover, the shape of the intensity build-up curves in NOESY is not as “sophisticated” as that in TOCSY and thus does not require a dense sampling.…”

Primary Structure of Glycans by NMR Spectroscopy

“…The NUS technique works very well when the sampling density is matched with the envelope of the decaying signal and any modulation caused by, e.g., one-bond 1 H, 13 C scalar couplings, being on the order of ∼ 150 Hz in carbohydrates. Thus, NUS 1 H, 13 C-HSQC NMR experiments with a coverage of 10% and 20% have been reported for poly- and oligosaccharides, respectively. , However, applying NUS to 1 H, 1 H-NOESY experiments is significantly more demanding due to the high dynamic range where spectra contain peaks of both high and low intensity. ,, Aliasing artifacts in NUS NMR spectra have been investigated and ways to minimize these have been proposed …”

“…398,399 However, applying NUS to 1 H, 1 H-NOESY experiments is significantly more demanding due to the high dynamic range where spectra contain peaks of both high and low intensity. 398,400,401 Aliasing artifacts in NUS NMR spectra have been investigated and ways to minimize these have been proposed. 402 5.3.2.…”