Stable Isotope Phosphate Labelling of Diverse Metabolites is Enabled by a Family of 18O‐Phosphoramidites
Stable isotope labelling is state‐of‐the‐art in quantitative mass spectrometry, yet often accessing the required standards is cumbersome and very expensive. Here, a unifying synthetic concept for 18O‐labelled phosphates is presented, based on a family of modified 18O2‐phosphoramidite reagents. This...
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Published in | Angewandte Chemie International Edition Vol. 61; no. 5 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Weinheim
Wiley Subscription Services, Inc
26.01.2022
John Wiley and Sons Inc |
Edition | International ed. in English |
Subjects | |
Online Access | Get full text |
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Summary: | Stable isotope labelling is state‐of‐the‐art in quantitative mass spectrometry, yet often accessing the required standards is cumbersome and very expensive. Here, a unifying synthetic concept for 18O‐labelled phosphates is presented, based on a family of modified 18O2‐phosphoramidite reagents. This toolbox offers access to major classes of biologically highly relevant phosphorylated metabolites as their isotopologues including nucleotides, inositol phosphates, ‐pyrophosphates, and inorganic polyphosphates. 18O‐enrichment ratios >95 % and good yields are obtained consistently in gram‐scale reactions, while enabling late‐stage labelling. We demonstrate the utility of the 18O‐labelled inositol phosphates and pyrophosphates by assignment of these metabolites from different biological matrices. We demonstrate that phosphate neutral loss is negligible in an analytical setup employing capillary electrophoresis electrospray ionisation triple quadrupole mass spectrometry.
A family of 18O2‐phosphoramidites facilitates synthetic access on gram‐scale to various isotopically pure 18O‐labelled phosphate products, like nucleotides, inositol phosphates, polyphosphates, and DNA. The utility of these 18O‐natural products is underlined in the assignment of various metabolites from biological matrices using capillary electrophoresis electrospray ionisation triple quadrupole mass spectrometry. |
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Bibliography: | https://doi.org/10.33774/chemrxiv‐2021‐0r9g7 . A previous version of this manuscript has been deposited on a preprint server A previous version of this manuscript has been deposited on a preprint server (https://doi.org/10.33774/chemrxiv‐2021‐0r9g7). |
ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.202112457 |