Spectral resolution is the key to unleashing the structural and dynamic information contained in NMR spectra. Fast magic-angle spinning (MAS) has recently revolutionized the spectroscopy of biomolecular solids. Herein, we report a further remarkable improvement in the resolution of the spectra of four fully protonated proteins and a small drug molecule by pushing the MAS rotation frequency higher (150 kHz) than the more routinely used 100 kHz. We observed a reduction in the average homogeneous linewidth by a factor of 1.5 and a decrease in the observed linewidth by a factor 1.25. We conclude that even faster MAS is highly attractive and increases mass sensitivity at a moderate price in overall sensitivity.
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http://dx.doi.org/10.1002/cbic.202000341 | DOI Listing |
J Pharm Sci
January 2025
Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000 Leuven, Belgium. Electronic address:
In order to evaluate the stability of an amorphous solid dispersion (ASD) it is crucial to be able to accurately determine whether the ASD components are homogeneously mixed or not. Several solid-state analysis techniques are at the disposal of the formulation scientist, such as for example modulated differential scanning calorimetry (mDSC) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). ssNMR is a robust, versatile, and accurate analysis technique with a large number of application possibilities.
View Article and Find Full Text PDFMisfolding and aggregation of proteins into amyloidogenic assemblies are key features of several metabolic and neurodegenerative diseases. Human insulin has long been known to form amyloid fibrils under various conditions, which affects its bioavailability and function. Clinically, insulin aggregation at recurrent injection sites poses a challenge for diabetic patients who rely on insulin therapy.
View Article and Find Full Text PDFACS Omega
January 2025
Science Division, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates.
Determining the structure of sitagliptin is crucial for ensuring its effectiveness and safety as a DPP-4 inhibitor used to treat type 2 diabetes. Accurate structure determination is vital for both drug development and maintaining quality control in manufacturing. This study integrates the advanced techniques of solid-state nuclear magnetic resonance (NMR) spectroscopy, three-dimensional (3D) electron diffraction, and density functional theory (DFT) calculations to investigate the structural intricacies of sitagliptin.
View Article and Find Full Text PDFJ Biomol NMR
January 2025
Research Unit Molecular Biophysics, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Robert- Rössle-Straße 10, 13125, Berlin, Germany.
Chemical shift assignments of large membrane proteins by solid-state NMR experiments are challenging. Recent advancements in sensitivity-enhanced pulse sequences, have made it feasible to acquire H-detected 4D spectra of these challenging protein samples within reasonable timeframes. However, obtaining unambiguous assignments remains difficult without access to side-chain chemical shifts.
View Article and Find Full Text PDFAnal Chem
January 2025
Experimental Physics III, TU Dortmund University, Dortmund 44227, Germany.
Spectral dispersion in low-field nuclear magnetic resonance (NMR) can significantly affect NMR spectral analysis, particularly when studying complex mixtures like metabolic profiling of biological samples. To address signal superposition in these spectra, we employed spectral editing with selective excitation pulses, proving it to be a suitable approach. Optimal control pulses were implemented in low-field NMR and demonstrated their capability to selectively excite and eliminate specific amino acids, such as phenylalanine and taurine, either individually or simultaneously.
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