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Planta Med 2018; 84(16): 1201-1212
DOI: 10.1055/a-0608-4870
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Advantages of Molecular Weight Identification during Native MS Screening

Ahad Khan
1   Griffith Institute for Drug Discovery, Griffith University, Brisbane, Australia
,
Anne Bresnick
2   Albert Einstein College of Medicine, Bronx, NY, USA
,
Sean Cahill
2   Albert Einstein College of Medicine, Bronx, NY, USA
,
Mark Girvin
2   Albert Einstein College of Medicine, Bronx, NY, USA
,
Steve Almo
2   Albert Einstein College of Medicine, Bronx, NY, USA
,
Ronald Quinn
1   Griffith Institute for Drug Discovery, Griffith University, Brisbane, Australia
› Author Affiliations
Further Information

Publication History

received 03 October 2017
revised 01 April 2018

accepted 11 April 2018

Publication Date:
09 May 2018 (online)

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Abstract

Native mass spectrometry detection of ligand-protein complexes allowed rapid detection of natural product binders of apo and calcium-bound S100A4 (a member of the metal binding protein S100 family), T cell/transmembrane, immunoglobulin (Ig), and mucin protein 3, and T cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibitory motif) domains precursor protein from extracts and fractions. Based on molecular weight common hits were detected binding to all four proteins. Seven common hits were identified as apigenin 6-C-β-D-glucoside 8-C-α-L-arabinoside, sweroside, 4′,5-dihydroxy-7-methoxyflavanone-6-C-rutinoside, loganin acid, 6-C-glucosylnaringenin, biochanin A 7-O-rutinoside and quercetin 3-O-rutinoside. Mass guided isolation and NMR identification of hits confirmed the mass accuracy of the ligand in the ligand-protein MS complexes. Thus, molecular weight ID from ligand-protein complexes by electrospray ionization Fourier transform mass spectrometry allowed rapid dereplication. Native mass spectrometry using electrospray ionization Fourier transform mass spectrometry is a tool for dereplication and metabolomics analysis.

Key words

dereplication - ligand-protein complex - metabolomics - molecular weight - native mass spectrometry

Supporting Information

    Hit detection and molecular weight determination of hits during native MS screening, the strategy for classification of the hits, detailed information of common hits and their biota sources, NMR spectra of the isolated common hits NP_358, NP_376, NP_434, NP_592, NP_564, NP_594, and NP_610, amino acid sequences of human S100A4 and TIGIT and mouse TIM3 proteins that were used for this project, determination of optimum screening concentrations of the proteins, gradient methods (timetable) for LLEF preparation, LC-LRMS and LC–HRMS analysis of extracts/fractions, optimum screening conditions of critical instrumental parameters, and the charge deconvolution method are available as Supporting Information.

  • Supporting Information
 

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