Δ-Myrtoxin-Mp1a is a Helical Heterodimer from the Venom of the Jack Jumper Ant that has Antimicrobial, Membrane-Disrupting, and Nociceptive Activities

Zoltan Dekan, Stephen J. Headey, Martin Scanlon, Brian A. Baldo, Tzong-Hsien Lee, Marie-Isabel Aguilar, Jennifer R. Deuis, Irina Vetter, Alysha G. Elliott, Maite Amado, Matthew A. Cooper, Dianne Alewood, Paul F. Alewood

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

Δ-Myrtoxin-Mp1a (Mp1a), a 49-residue heterodimeric peptide from the venom of Myrmecia pilosula, comprises a 26-mer A chain and a 23-mer B chain connected by two disulfide bonds in an antiparallel arrangement. Combination of the individual synthetic chains through aerial oxidation remarkably resulted in the self-assembly of Mp1a as a homogenous product without the need for directed disulfide-bond formation. NMR analysis revealed a well-defined, unique structure containing an antiparallel α-helix pair. Dual polarization interferometry (DPI) analysis showed strong interaction with supported lipid bilayers and insertion within the bilayers. Mp1a caused non-specific Ca2+ influx in SH-SY5Y cells with a half maximal effective concentration (EC50) of 4.3 μm. Mp1a also displayed broad-spectrum antimicrobial activity, with the highest potency against Gram-negative Acinetobacter baumannii (MIC 25 nm). Intraplantar injection (10 μm) in mice elicited spontaneous pain and mechanical allodynia. Single- and two-chain mimetics of Mp1a revealed functional selectivity.

Original languageEnglish
Pages (from-to)8495-8499
Number of pages6
JournalAngewandte Chemie - International Edition
Volume56
Issue number29
DOIs
Publication statusPublished - 10 Jul 2017

Keywords

  • antimicrobial peptides
  • nociceptive pain
  • peptides
  • self-assembly
  • toxins

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