Stable Isotope Phosphate Labelling of Diverse Metabolites is Enabled by a Family of 18O‐Phosphoramidites. Issue 5 (23rd November 2021)

• Record Type: Journal Article
• Authors: Haas, Thomas M.; Mundinger, Stephan; Qiu, Danye; Jork, Nikolaus; Ritter, Kevin; Dürr‐Mayer, Tobias; Ripp, Alexander; Saiardi, Adolfo; Schaaf, Gabriel; Jessen, Henning J.
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-23
• Subjects: capillary electrophoresis -- mass spectrometry -- nucleotides -- phosphorylation -- stable isotope labelling; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202112457
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 18 O‐labelled phosphates is presented, based on a family of modified 18 O2 ‐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. 18 O‐enrichment ratios >95 % and good yields are obtained consistently in gram‐scale reactions, while enabling late‐stage labelling. We demonstrate the utility of the 18 O‐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. Abstract : A family of 18 O2 ‐phosphoramidites facilitates synthetic access on gram‐scale to various isotopically pure 18 O‐labelled phosphate products, like nucleotides, inositol phosphates, polyphosphates, and DNA. The utility of these 18 O‐natural products is underlined in the assignment of various metabolites from biological matrices using capillary electrophoresis electrospray ionisation triple quadrupole mass spectrometry.