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Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena.
Peptides. 2013 Jun; 44:40-6.P

Abstract

The spider venom peptide Huwentoxin-IV (HwTx-IV) 1 is a potent antagonist of hNav1.7 (IC50 determined herein as 17 ± 2 nM). Nav1.7 is a voltage-gated sodium channel involved in the generation and conduction of neuropathic and nociceptive pain signals. We prepared a number of HwTx-IV analogs as part of a structure-function study into Nav1.7 antagonism. The inhibitory potency of these analogs was determined by automated electrophysiology and is reported herein. In particular, the native residues Glu(1), Glu(4), Phe(6) and Tyr(33) were revealed as important activity modulators and several peptides bearing mutations in these positions showed significantly increased potency on hNav1.7 while maintaining the original selectivity profile of the wild-type peptide 1 on hNav1.5. Peptide 47 (Gly(1), Gly(4), Trp(33)-HwTx) demonstrated the largest potency increase on hNav1.7 (IC50 0.4 ± 0.1 nM).

Authors+Show Affiliations

MedImmune, Cambridge, United Kingdom. revellj@medimmune.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23523779

Citation

Revell, Jefferson D., et al. "Potency Optimization of Huwentoxin-IV On hNav1.7: a Neurotoxin TTX-S Sodium-channel Antagonist From the Venom of the Chinese Bird-eating Spider Selenocosmia Huwena." Peptides, vol. 44, 2013, pp. 40-6.
Revell JD, Lund PE, Linley JE, et al. Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. Peptides. 2013;44:40-6.
Revell, J. D., Lund, P. E., Linley, J. E., Metcalfe, J., Burmeister, N., Sridharan, S., Jones, C., Jermutus, L., & Bednarek, M. A. (2013). Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. Peptides, 44, 40-6. https://doi.org/10.1016/j.peptides.2013.03.011
Revell JD, et al. Potency Optimization of Huwentoxin-IV On hNav1.7: a Neurotoxin TTX-S Sodium-channel Antagonist From the Venom of the Chinese Bird-eating Spider Selenocosmia Huwena. Peptides. 2013;44:40-6. PubMed PMID: 23523779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potency optimization of Huwentoxin-IV on hNav1.7: a neurotoxin TTX-S sodium-channel antagonist from the venom of the Chinese bird-eating spider Selenocosmia huwena. AU - Revell,Jefferson D, AU - Lund,Per-Eric, AU - Linley,John E, AU - Metcalfe,Jacky, AU - Burmeister,Nicole, AU - Sridharan,Sudharsan, AU - Jones,Clare, AU - Jermutus,Lutz, AU - Bednarek,Maria A, Y1 - 2013/03/19/ PY - 2012/12/05/received PY - 2013/03/06/revised PY - 2013/03/06/accepted PY - 2013/3/26/entrez PY - 2013/3/26/pubmed PY - 2014/1/1/medline SP - 40 EP - 6 JF - Peptides JO - Peptides VL - 44 N2 - The spider venom peptide Huwentoxin-IV (HwTx-IV) 1 is a potent antagonist of hNav1.7 (IC50 determined herein as 17 ± 2 nM). Nav1.7 is a voltage-gated sodium channel involved in the generation and conduction of neuropathic and nociceptive pain signals. We prepared a number of HwTx-IV analogs as part of a structure-function study into Nav1.7 antagonism. The inhibitory potency of these analogs was determined by automated electrophysiology and is reported herein. In particular, the native residues Glu(1), Glu(4), Phe(6) and Tyr(33) were revealed as important activity modulators and several peptides bearing mutations in these positions showed significantly increased potency on hNav1.7 while maintaining the original selectivity profile of the wild-type peptide 1 on hNav1.5. Peptide 47 (Gly(1), Gly(4), Trp(33)-HwTx) demonstrated the largest potency increase on hNav1.7 (IC50 0.4 ± 0.1 nM). SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/23523779/Potency_optimization_of_Huwentoxin_IV_on_hNav1_7:_a_neurotoxin_TTX_S_sodium_channel_antagonist_from_the_venom_of_the_Chinese_bird_eating_spider_Selenocosmia_huwena_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(13)00086-7 DB - PRIME DP - Unbound Medicine ER -