Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds
Name
nihms-1003344.pdf
Description
Accepted version
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2.35 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Roos, Matthias
Wang, Tuo
Shcherbakov, Alexander Aleksandrovich
Hong, Mei
Alternative Title
Fast Magic-Angle-Spinning [superscript 19]F Spin Exchange NMR for Determining Nanometer [superscript 19]F-[superscript 19]F Distances in Proteins and Pharmaceutical Compounds
Date Issued
February 2018
Journal
Journal of Physical Chemistry B
Publisher
American Chemical Society (ACS)
Citation
Roos, Matthias, et al., "Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds." Journal of Physical Chemistry B 122, 11 (Feb. 2018): p. 2900-11 doi 10.1021/ACS.JPCB.8B00310 ©2018 Author(s)
Version
Author's final manuscript
Abstract
Internuclear distances measured using NMR provide crucial constraints of three-dimensional structures but are often restricted to about 5 Å due to the weakness of nuclear-spin dipolar couplings. For studying macromolecular assemblies in biology and materials science, distance constraints beyond 1 nm will be extremely valuable. Here we present an extensive and quantitative analysis of the feasibility of [superscript 19]F spin exchange NMR for precise and robust measurements of interatomic distances up to 1.6 nm at a magnetic field of 14.1 T, under 20-40 kHz magic-angle spinning (MAS). The measured distances are comparable to those achievable from paramagnetic relaxation enhancement but have higher precision, which is better than ±1 Å for short distances and ±2 Å for long distances. For [superscript 19]F spins with the same isotropic chemical shift but different anisotropic chemical shifts, intermediate MAS frequencies of 15-25 kHz without 1H irradiation accelerate spin exchange. For spectrally resolved [superscript 19]F-[superscript 19]F spin exchange, [superscript 1]H-[superscript 19]F dipolar recoupling significantly speeds up [superscript 19]F-[superscript 19]F spin exchange. On the basis of data from five fluorinated synthetic, pharmaceutical, and biological compounds, we obtained two general curves for spin exchange between CF groups and between CF[subscript 3] and CF groups. These curves allow [superscript 19]F-[superscript 19]F distances to be extracted from the measured spin exchange rates after taking into account [superscript 19]F chemical shifts. These results demonstrate the robustness of [superscript 19]F spin exchange NMR for distance measurements in a wide range of biological and chemical systems.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/ACS.JPCB.8B00310
