Development of DIMEN. (a) Schematic representation of metabolomes and purpose of DIMEN for the characterization of known, LC-MS visible (light gray) and LC-MS invisible (dark gray) molecules. (b) Glycosides of the dideoxy sugar ascarylose are combined with diverse primary metabolic building blocks in C. elegans. (c) Structure of solid-support, alkyne capture for enrichment and reporter-ion installation (ACER) resin (1), and alkyne probe ascr#3-YNE (3), which mimics ascr#3 (2), a precursor upstream of the biosynthesis of diverse signaling molecules. (d) Schematic overview of DIMEN analysis. C. elegans are grown with and without alkyne-labeled probe (blue star) and extracted. Probe is added to unlabeled samples before enrichment using the ACER resin. Enriched metabolomes are analyzed via LC-HRMS/MS to detect PDMs, e.g., ascr#3-LNK (4) and icas#3-LNK (5).