摘要：SummaryAnts (Hymenoptera: Formicidae) are familiar inhabitants of most terrestrial environments. Although we are aware of the ability of many species to sting, knowledge of ant venom chemistry remains limited. Herein, we describe the discovery and characterization of anO-linked glycopeptide (Mg7a) as a major component of the venom of the antMyrmecia gulosa. Electron transfer dissociation and higher-energy collisional dissociation tandem mass spectrometry were used to localize three α-N-acetylgalactosaminyl residues (α-GalNAc) present on the 63-residue peptide. To allow for functional studies, we synthesized the full-length glycosylated peptide via solid-phase peptide synthesis, combined with diselenide–selenoester ligation-deselenization chemistry. We show that Mg7a is paralytic and lethal to insects, and triggers pain behavior and inflammation in mammals, which it achieves through a membrane-targeting mode of action. Deglycosylation of Mg7a renders it insoluble in aqueous solution, suggesting a key solubilizing role of theO-glycans.Graphical abstractDisplay OmittedHighlights•The 63-amino acid glycopeptide Mg7a is a major component ofMyrmecia gulosavenom•Mg7a is insecticidal and causes pain behavior and inflammation in mice•Mg7a targets cell membranes causing a leak in ion conductance•Glycosylation is important for Mg7a solubilityNatural product chemistry; Biomolecules; Neuroscience
