Fernandez Diaz-Rullo, Fernando, Zamberlan, Francesco, Mewis, Ryan E. et al. (7 more authors) (2017) Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1H NMR spectroscopy. Bioorganic and Medicinal Chemistry. ISSN 0968-0896
Abstract
Hyperpolarization enhances the intensity of the NMR signals of a molecule, whose in vivo metabolic fate can be monitored by MRI with higher sensitivity. SABRE is a hyperpolarization technique that could potentially be used to image nitric oxide (NO) production in vivo. This would be very important, because NO dysregulation is involved in several pathologies, including cardiovascular ones. The nitric oxide synthase (NOS) pathway leads to NO production via conversion of l-arginine into l-citrulline. NO is a free radical gas with a short half-life in vivo (≈5s), therefore direct NO quantification is challenging. An indirect method - based on quantifying conversion of an l-Arg- to l-Cit-derivative by 1H NMR spectroscopy - is herein proposed. A small library of pyridyl containing l-Arg derivatives was designed and synthesised. In vitro tests showed that compounds 4a-j and 11a-c were better or equivalent substrates for the eNOS enzyme (NO2 - production=19-46μM) than native l-Arg (NO2 - production=25μM). Enzymatic conversion of l-Arg to l-Cit derivatives could be monitored by 1H NMR. The maximum hyperpolarization achieved by SABRE reached 870-fold NMR signal enhancement, which opens up exciting future perspectives of using these molecules as hyperpolarized MRI tracers in vivo.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors |
Keywords: | Hyperpolarization,l-Arginine,MRI,Real-time imaging,SABRE |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 12 Apr 2017 10:00 |
Last Modified: | 27 Nov 2024 00:29 |
Published Version: | https://doi.org/10.1016/j.bmc.2017.03.041 |
Status: | Published online |
Refereed: | Yes |
Identification Number: | 10.1016/j.bmc.2017.03.041 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:114993 |
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Description: Synthesis and hyperpolarisation of eNOS substrates for quantification of NO production by 1 H NMR spectroscopy
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