Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7

Kathleen Yin; Jennifer R Deuis; Zoltan Dekan; Ai-Hua Jin; Paul F Alewood; Glenn F King; Volker Herzig; Irina Vetter

doi:10.3390/biomedicines8020037

Back

Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7

Journal article

Open access

Peer reviewed

Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7

Kathleen Yin, Jennifer R Deuis, Zoltan Dekan, Ai-Hua Jin, Paul F Alewood, Glenn F King, Volker Herzig and Irina Vetter

Biomedicines, Vol.8(2), 37

2020

DOI: https://doi.org/10.3390/biomedicines8020037

Files and links (2)

pdf

PDF - Published Version (Open Access)896.43 kBDownload View

Published VersionPDF - Published Version (Open Access)CC BY V4.0, Open Access

url

https://doi.org/10.3390/biomedicines8020037View

Published Version

Abstract

sodium channel

NaV1.7

NaV1.8

venom

spider

peptide

Spider venom is a novel source of disulfide-rich peptides with potent and selective activity at voltage-gated sodium channels (NaV). Here, we describe the discovery of μ-theraphotoxin-Pme1a and μ/δ-theraphotoxin-Pme2a, two novel peptides from the venom of the Gooty Ornamental tarantula Poecilotheria metallica that modulate NaV channels. Pme1a is a 35 residue peptide that inhibits NaV1.7 peak current (IC50 334±114 nM) and shifts the voltage dependence of activation to more depolarised membrane potentials (V1/2 activation: Δ = +11.6 mV). Pme2a is a 33 residue peptide that delays fast inactivation and inhibits NaV1.7 peak current (EC50 > 10 μM). Synthesis of a [+22K]Pme2a analogue increased potency at NaV1.7 (IC50 5.6±1.1 μM) and removed the effect of the native peptide on fast inactivation, indicating that a lysine at position 22 (Pme2a numbering) is important for inhibitory activity. Results from this study may be used to guide the rational design of spider venom-derived peptides with improved potency and selectivity at NaV channels in the future.

Details

Title: Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7
Authors: Kathleen Yin (Author) - Macquarie University
Jennifer R Deuis (Author) - University of Queensland
Zoltan Dekan (Author) - University of Queensland
Ai-Hua Jin (Author) - University of Queensland
Paul F Alewood (Author) - University of Queensland
Glenn F King (Author) - University of Queensland
Volker Herzig (Author) - University of the Sunshine Coast - School of Science and Engineering
Irina Vetter (Author) - University of Queensland
Publication details: Biomedicines, Vol.8(2), 37; 9
Publisher: MDPI AG
Date published: 2020
DOI: 10.3390/biomedicines8020037
ISSN: 2227-9059
Copyright note: Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450976702621
Output Type: Journal article

Metrics

7 File views/ downloads

92 Record Views

7 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Medicine, Research & Experimental; Pharmacology & Pharmacy

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites