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

doi:10.1002/anie.201703360

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 journal › Article › Research › peer-review

27 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 language	English
Pages (from-to)	8495-8499
Number of pages	6
Journal	Angewandte Chemie - International Edition
Volume	56
Issue number	29
DOIs	https://doi.org/10.1002/anie.201703360
Publication status	Published - 10 Jul 2017

Keywords

antimicrobial peptides
nociceptive pain
peptides
self-assembly
toxins

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10.1002/anie.201703360

Cite this

Dekan, Z., Headey, S. J., Scanlon, M., Baldo, B. A., Lee, T.-H., Aguilar, M.-I., Deuis, J. R., Vetter, I., Elliott, A. G., Amado, M., Cooper, M. A., Alewood, D., & Alewood, P. F. (2017). 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 - International Edition, 56(29), 8495-8499. https://doi.org/10.1002/anie.201703360

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

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",

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

year = "2017",

month = jul,

day = "10",

doi = "10.1002/anie.201703360",

language = "English",

volume = "56",

pages = "8495--8499",

journal = "Angewandte Chemie - International Edition",

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Dekan, Z, Headey, SJ, Scanlon, M, Baldo, BA, Lee, T-H , Aguilar, M-I, Deuis, JR, Vetter, I, Elliott, AG, Amado, M, Cooper, MA, Alewood, D & Alewood, PF 2017, '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 - International Edition, vol. 56, no. 29, pp. 8495-8499. https://doi.org/10.1002/anie.201703360

Δ-Myrtoxin-Mp1a is a Helical Heterodimer from the Venom of the Jack Jumper Ant that has Antimicrobial, Membrane-Disrupting, and Nociceptive Activities. / Dekan, Zoltan; Headey, Stephen J.; Scanlon, Martin et al.
In: Angewandte Chemie - International Edition, Vol. 56, No. 29, 10.07.2017, p. 8495-8499.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Δ-Myrtoxin-Mp1a is a Helical Heterodimer from the Venom of the Jack Jumper Ant that has Antimicrobial, Membrane-Disrupting, and Nociceptive Activities

AU - Dekan, Zoltan

AU - Headey, Stephen J.

AU - Scanlon, Martin

AU - Baldo, Brian A.

AU - Lee, Tzong-Hsien

AU - Aguilar, Marie-Isabel

AU - Deuis, Jennifer R.

AU - Vetter, Irina

AU - Elliott, Alysha G.

AU - Amado, Maite

AU - Cooper, Matthew A.

AU - Alewood, Dianne

AU - Alewood, Paul F.

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N2 - 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.

AB - 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.

KW - antimicrobial peptides

KW - nociceptive pain

KW - peptides

KW - self-assembly

KW - toxins

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DO - 10.1002/anie.201703360

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VL - 56

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ER -

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

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Keywords

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Selective targeting of microbes by peptides of the innate immune system

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

Abstract

Keywords

Access to Document

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Selective targeting of microbes by peptides of the innate immune system

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