Next Article in Journal
Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands
Next Article in Special Issue
European Medicinal Leeches—New Roles in Modern Medicine
Previous Article in Journal
The Co-Expression of Programmed Death-Ligand 1 (PD-L1) in Untreated EGFR-Mutated Metastatic Lung Adenocarcinoma
Open AccessArticle

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

1
Centre for Health Informatics, Australian Institute of Health Innovation, Macquarie University, North Ryde, NSW 2109, Australia
2
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
3
School of Science & Engineering, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia
4
School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomedicines 2020, 8(2), 37; https://doi.org/10.3390/biomedicines8020037
Received: 22 January 2020 / Revised: 13 February 2020 / Accepted: 17 February 2020 / Published: 19 February 2020
(This article belongs to the Special Issue Animal Venoms–Curse or Cure?)
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. View Full-Text
Keywords: sodium channel; NaV1.7; NaV1.8; venom; spider; peptide sodium channel; NaV1.7; NaV1.8; venom; spider; peptide
Show Figures

Graphical abstract

MDPI and ACS Style

Yin, K.; Deuis, J.R.; Dekan, Z.; Jin, A.-H.; Alewood, P.F.; King, G.F.; Herzig, V.; Vetter, I. Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7. Biomedicines 2020, 8, 37. https://doi.org/10.3390/biomedicines8020037

AMA Style

Yin K, Deuis JR, Dekan Z, Jin A-H, Alewood PF, King GF, Herzig V, Vetter I. Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7. Biomedicines. 2020; 8(2):37. https://doi.org/10.3390/biomedicines8020037

Chicago/Turabian Style

Yin, Kathleen; Deuis, Jennifer R.; Dekan, Zoltan; Jin, Ai-Hua; Alewood, Paul F.; King, Glenn F.; Herzig, Volker; Vetter, Irina. 2020. "Addition of K22 Converts Spider Venom Peptide Pme2a from an Activator to an Inhibitor of NaV1.7" Biomedicines 8, no. 2: 37. https://doi.org/10.3390/biomedicines8020037

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop