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bioRxiv · 10.1101/2022.07.04.498692

Chiral Derivatization-enabled Discrimination and Visualization of Proteinogenic Amino Acids by Ion Mobility Mass Spectrometry

Xie, C.·Chen, Y.·Wang, X.·Song, Y.·Shen, Y.·Diao, X.·Zhu, L.·Wang, J.·Cai, Z.
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Abstract

The importance of chiral amino acids (AAs) in living organisms has been widely recognized since the discovery of endogenous D-AAs as potential biomarkers in several metabolic disorders. Chiral analysis by ion mobility spectrometry-mass spectrometry (IMS-MS) has the advantages of high speed and sensitivity but is still in its infancy. Here, a N-(2,4-dinitro-5-fluorophenyl)-L-alaninamide (FDAA) derivatization is combined with trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) for chiral AA analysis. For the first time, we demonstrate the simultaneous separation of 19 pairs of chiral proteinogenic AAs in a single fixed condition TIMS-MS run. The utility of this approach presents for mouse brain extracts by direct-infusion TIMS-MS. The robust separation ability in complex biological sample was proven in MALDI TIMS mass spectrometry imaging (MSI) as well by directly depositing 19 pairs of AAs on a tissue slide following on-tissue derivatization. In addition, endogenous chiral amino acids were also detected and distinguished. The developed methods show compelling application prospects in biomarker discovery and biological research. Entry for the Table of Contents O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/498692v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@19af718org.highwire.dtl.DTLVardef@d457d7org.highwire.dtl.DTLVardef@d2f932org.highwire.dtl.DTLVardef@e64831_HPS_FORMAT_FIGEXP M_FIG C_FIG The combination of chiral derivatization and trapped ion mobility-mass spectrometry provides the first insights into the separation of 19 pairs of chiral proteinogenic D/L-amino acids in a single run and further visualization of chiral amino acids under complex biological matrix.

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Xie, C., Chen, Y., Wang, X., Song, Y., Shen, Y., Diao, X., Zhu, L., Wang, J., Cai, Z.. 2022-07-05. Chiral Derivatization-enabled Discrimination and Visualization of Proteinogenic Amino Acids by Ion Mobility Mass Spectrometry. https://doi.org/10.1101/2022.07.04.498692

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