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Angew Chem Int Ed Engl. 2017 Jul 10;56(29):8495-8499. doi: 10.1002/anie.201703360. Epub 2017 Jun 13.

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

Author information

1
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
2
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
3
Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, St. Leonards, NSW, 2065, Australia.
4
Department of Biochemistry and Molecular Biology, Monash University, Wellington Rd, Clayton, Vic, 3800, Australia.

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.

KEYWORDS:

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

PMID:
28513074
DOI:
10.1002/anie.201703360
[Indexed for MEDLINE]

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