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
