A novel method for the determination of the relative stereochemistry of six-membered chairlike ring molecules by residual dipolar couplings is presented. C-H residual dipolar couplings were used to investigate the relative stereochemistry of 4,6-O-ethylidene-d-glucopyranose. For this and similar systems it is not necessary to acquire redundant dipolar couplings and to calculate the orientation order tensor. The presented methodology is a paradigmatic leap for the determination of the relative stereochemistry or remote stereochemistry in this kind of fused ring system. Residual dipolar coupling data were collected by 1D and 2D direct-measurement heteronuclear multiple quantum coherence (HMQC) spectroscopy. It was demonstrated that direct measurement of HMQC was quick and accurate for small molecules at natural abundance.
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Materials (Basel)
December 2024
Physics Faculty, West University of Timisoara, Bd. V. Parvan, No. 4, 300223 Timisoara, Romania.
Three elastomer samples were prepared using GS530SP01K1 silicone rubber (ProChima). The samples included pure silicone rubber (SR), a silicone rubber-graphene composite (SR-GR), and a silicone rubber-magnetite composite (SR-FeO). The magnetite was synthesized via chemical precipitation but was not washed to remove residual ions.
View Article and Find Full Text PDFJ Biomol NMR
December 2024
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892-0520, USA.
Inclusion of residual dipolar couplings (RDCs) during the early rounds of protein structure determination requires use of a floating alignment tensor or knowledge of the alignment tensor strength and rhombicity. For proteins with interdomain motion, such analysis can falsely hide the presence of domain dynamics. We demonstrate for three proteins, maltotriose-ligated maltose binding protein (MBP), Ca-ligated calmodulin, and a monomeric N-terminal deletion mutant of the SARS-CoV-2 Main Protease, MPro, that good alignment tensor estimates of their domains can be obtained from RDCs measured for residues that are identified as α-helical based on their chemical shifts.
View Article and Find Full Text PDFACS Med Chem Lett
November 2024
Medicine Design, Pfizer Inc., 1 Portland Street, Cambridge, Massachusetts 02139, United States.
To gain further insight into the conformational properties of small cyclic peptides that bind to the G-protein coupled receptor C5aR1, we report here for the first time the elucidation of three peptide solution conformations using residual dipolar couplings and NMR temperature coefficients. Each of these peptides varies by at least one amino acid, adopts a different intramolecular hydrogen bonding pattern, and has a different solution conformation. The solution conformations were used in combination with a homology structure of C5aR1 as a design template for increasing the potency of peptide leads for the C5a receptor.
View Article and Find Full Text PDFNature
November 2024
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Quantum computation and simulation rely on long-lived qubits with controllable interactions. Trapped polar molecules have been proposed as a promising quantum computing platform, offering scalability and single-particle addressability while still leveraging inherent complexity and strong couplings of molecules. Recent progress in the single quantum state preparation and coherence of the hyperfine-rotational states of individually trapped molecules allows them to serve as promising qubits, with intermolecular dipolar interactions creating entanglement.
View Article and Find Full Text PDFNMR Biomed
January 2025
Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong.
Quantitative magnetization transfer (MT) imaging enables noninvasive characterization of the macromolecular environment of tissues. However, recent work has highlighted that the quantification of MT parameters using saturation radiofrequency (RF) pulses exhibits orientation dependence in ordered tissue structures, potentially confounding its clinical applications. Notably, in tissues with ordered structures, such as articular cartilage and myelin, the residual dipolar coupling (RDC) effect can arise owing to incomplete averaging of dipolar-dipolar interactions of water protons.
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