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

Angewandte Chemie
Zoltan DekanPaul F Alewood

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.

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Citations

Jul 6, 2018·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Troy WanandyMichael D Wiese
Dec 19, 2017·Chembiochem : a European Journal of Chemical Biology·Kathrin Lang
Jun 15, 2020·Biochemical Pharmacology·Volker HerzigGlenn F King
Dec 22, 2020·ACS Pharmacology & Translational Science·Axel TouchardChristophe Duplais
Jun 3, 2021·Clinical Reviews in Allergy & Immunology·Troy WanandyMichael D Wiese
Nov 15, 2020·Toxicon : Official Journal of the International Society on Toxinology·Larissa Queiroz RochaAlice Maria Costa Martins
Aug 31, 2020·Toxicon : Official Journal of the International Society on Toxinology·Hilania V Dodou LimaGandhi Rádis-Baptista

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