Ants (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 an O-linked
glycopeptide (Mg7a) as a major component of the
venom of the ant Myrmecia 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 the O-
glycans.