A pain-causing and paralytic ant venom glycopeptide

Summary 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.
Graphical abstract
Highlights • The 63-amino acid glycopeptide Mg7a is a major component of Myrmecia gulosa venom • 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 solubility
Natural product chemistry; Biomolecules; Neuroscience