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  Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP

Stevanato, G., Ding, Y., Mamone, S., Jagtap, A. P., Korchak, S., & Glöggler, S. (2023). Real-Time Pyruvate Chemical Conversion Monitoring Enabled by PHIP. Journal of the American Chemical Society, 145(10), 5864-5871. doi:10.1021/jacs.2c13198.

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 Creators:
Stevanato, Gabriele1, Author           
Ding, Yonghong1, Author           
Mamone, Salvatore1, Author           
Jagtap, Anil P.1, Author           
Korchak, Sergey1, Author           
Glöggler, Stefan1, Author           
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1Research Group of NMR Signal Enhancement, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350277              

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 Abstract: In recent years, parahydrogen-induced polarization side arm hydrogenation (PHIP-SAH) has been applied to hyperpolarize [1-13C]pyruvate and map its metabolic conversion to [1-13C]lactate in cancer cells. Developing on our recent MINERVA pulse sequence protocol, in which we have achieved 27% [1-13C]pyruvate carbon polarization, we demonstrate the hyperpolarization of [1,2-13C]pyruvate (∼7% polarization on each 13C spin) via PHIP-SAH. By altering a single parameter in the pulse sequence, MINERVA enables the signal enhancement of C1 and/or C2 in [1,2-13C]pyruvate with the opposite phase, which allows for the simultaneous monitoring of different chemical reactions with enhanced spectral contrast or for the same reaction via different carbon sites. We first demonstrate the ability to monitor the same enzymatic pyruvate to lactate conversion at 7T in an aqueous solution, in vitro, and in-cell (HeLa cells) via different carbon sites. In a second set of experiments, we use the C1 and C2 carbon positions as spectral probes for simultaneous chemical reactions: the production of acetate, carbon dioxide, bicarbonate, and carbonate by reacting [1,2-13C]pyruvate with H2O2 at a high temperature (55 °C). Importantly, we detect and characterize the intermediate 2-hydroperoxy-2-hydroxypropanoate in real time and at high temperature.

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Language(s): eng - English
 Dates: 2023-03-012023-03-15
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1021/jacs.2c13198
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Project name : The authors thank the Max Planck Society for generous funding. This project received funding from the Deutsche Forschungsgemeinschaft (DFG) (Grants 418416679, 426677227, and 450146057) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 949180). Open access funded by Max Planck Society.
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Project name : HyperULFNMR
Grant ID : 949180
Funding program : Horizon 2020 (H2020)
Funding organization : European Commission (EC)

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Title: Journal of the American Chemical Society
  Other : JACS
  Abbreviation : J. Am. Chem. Soc.
Source Genre: Journal
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Publ. Info: Washington, DC : American Chemical Society
Pages: - Volume / Issue: 145 (10) Sequence Number: - Start / End Page: 5864 - 5871 Identifier: ISSN: 0002-7863
CoNE: https://pure.mpg.de/cone/journals/resource/954925376870