Chemical Science
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derivative (ꢀ)-76, are powerful probes for quantifying intracel- EPSRC and the MRC through the Systems Approaches to
lular levels of endogenous PtdInsPns. These compounds will be Biomedical Sciences Doctoral Training Centre (EP/G037280/1)
important in furthering our understanding of the biological role with additional support from AstraZeneca. We thank Dr
of these important signalling molecules.
James Wickens from the CRL Mass Spectrometry Research
Facility, Dr Barbara O'Dell and Tina Jackson from the CRL NMR
Research Facility at the University of Oxford. S. J. C. thanks St
Hugh's College, Oxford, for research support.
Conclusions
In summary, we have developed robust, and efficient synthetic
routes towards saturated and unsaturated PtdIns4P and
PtdIns5P derivatives. To our knowledge, this work represents
both the rst synthesis of unsaturated PtdIns4P derivatives that
relies on a desymmetrisation strategy,28–30 and the most efficient
synthesis of enantiomerically pure PtdIns5P described so far,
with an overall yield of 20%.35,56,57 As a result of the high yielding
enzymatic desymmetrisation strategy employed, these routes
are amenable to the synthesis of a versatile set of stable-isotope
labelled PtdInsP derivatives. This is demonstrated through the
optimisation of a large-scale synthesis of deuterated myo-
inositol, and the synthesis of a set of deuterated PtdIns4P and
PtdIns5P derivatives. In addition to the deuterated analogues
synthesised herein, this synthetic route could be readily
extended to the synthesis of [13C]-labelled PtdInsP derivatives.25
We have demonstrated that the stable isotope-labelled
PtdInsPn probes synthesised represent powerful tools for quan-
tifying PtdInsPn levels in a cellular setting. Application of these
compounds to MCF7 cells enable quantication of endogenous
PtdInsPn levels in a manner that was previously impossible.
Notes and references
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There are no conicts to declare.
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Acknowledgements
A. M. J. thanks the EPSRC and AstraZeneca for the award of an 26 L. Zhang, L. Shi, Y. Shen, Y. Miao, M. Wei, N. Qian, Y. Liu
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2556 | Chem. Sci., 2021, 12, 2549–2557
© 2021 The Author(s). Published by the Royal Society of Chemistry