A reexamination of poneratoxin from the venom of the bullet ant Paraponera clavata

摘要: Abstract In 1991, Piek et al. [45] described a voltage-gated sodium channel (VGSC) modifier from “bullet ant” ( Paraponera clavata ) venom they called poneratoxin (PoTx). Using UV chromatography and Edman degradation showed two “identical peptides” of 25 residues. We reinvestigated PoTx using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-TMS). De novo sequencing the peptides were actually structurally different peptides: originally glycyl pro-peptide -PoTx) that lacks C-terminus amidation. examined P. geographical locations discovered additional analogs: an A23E substitution analog D22N; A23V substitutions analog. tested these three natural analogs on mammalian sensory channel, Na v 1.7, whole cell voltage-clamp. each induced slowly activating currents in response to small depolarizing steps sustained due blockade inactivation, similar previously skeletal muscle [19] . Glycyl -PoTx had same potency efficacy as PoTx. PoTx, with decrease both C-terminal net positive charge hydrophobicity, eight-fold reduction compared contrast, increase nearly five-fold found changes caused significant change potency.