Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds
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...
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2020
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| Online Access: | https://hdl.handle.net/1721.1/125915 |
| _version_ | 1826199425762983936 |
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| author | Roos, Matthias Wang, Tuo Shcherbakov, Alexander Aleksandrovich Hong, Mei |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Roos, Matthias Wang, Tuo Shcherbakov, Alexander Aleksandrovich Hong, Mei |
| author_sort | Roos, Matthias |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:19:42Z |
| format | Article |
| id | mit-1721.1/125915 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:19:42Z |
| publishDate | 2020 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1259152022-09-27T18:46:32Z Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds 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 Roos, Matthias Wang, Tuo Shcherbakov, Alexander Aleksandrovich Hong, Mei Massachusetts Institute of Technology. Department of Chemistry 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. NIH (grant no. GM066976) German National Academy of Science Leopoldina Postdoctoral Fellowship (grant no. LPDS-2017–14) 2020-06-22T17:12:38Z 2020-06-22T17:12:38Z 2018-02 2019-12-18T14:54:49Z Article http://purl.org/eprint/type/JournalArticle 1520-6106 https://hdl.handle.net/1721.1/125915 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) en 10.1021/ACS.JPCB.8B00310 Journal of Physical Chemistry B Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Roos, Matthias Wang, Tuo Shcherbakov, Alexander Aleksandrovich Hong, Mei Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title | Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title_full | Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title_fullStr | Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title_full_unstemmed | Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title_short | Fast Magic-Angle-Spinning 19F Spin Exchange NMR for Determining Nanometer 19F-19F Distances in Proteins and Pharmaceutical Compounds |
| title_sort | fast magic angle spinning 19f spin exchange nmr for determining nanometer 19f 19f distances in proteins and pharmaceutical compounds |
| url | https://hdl.handle.net/1721.1/125915 |
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