LAUSR

To date, advanced chemical biology tools for chemoselective extraction of metabolites are limited. In this study, unique coral-like polymer particles were synthesized via high concentrations of 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS), which are usually used as condensation agents. The polymers can wrap or adhere Fe3O4 nanoparticles (Fe3O4-NPs) to form polymer magnetic microparticles (PMMPs). With abundant NHS-activated moieties on their surface, the coral-like PMMPs could be modified by cystamine for the chemoselective extraction of phosphate/carboxylate anion metabolites from complex biological samples. Finally, 97 metabolites including nucleotides, phosphates, phosphate sugars, carboxylate sugars, and organic acids were extracted and identified from serum, tissues, and cells. These metabolites are involved in four major metabolic pathways including glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and nucleotide metabolism. This study has provided a cost-effective and easy-to-implement preparation of PMMPs with a robust chemoselective extraction ability and versatile applications.