Title: Drosotoxin, a selective inhibitor of tetrodotoxin-resistant sodium channels
Authors: Zhu, Shunyi ×
Gao, Bin
Deng, Meichun
Yuan, Yuzhe
Luo, Lan
Peigneur, Steve
Xiao, Yucheng
Liang, Songping
Tytgat, Jan #
Issue Date: Oct-2010
Publisher: Elsevier
Series Title: Biochemical Pharmacology vol:80 issue:8 pages:1296-1302
Abstract: The design of animal toxins with high target selectivity has long been a goal in protein engineering. Based on evolutionary relationship between the Drosophila antifungal defensin (drosomycin) and scorpion depressant Na+ channel toxins, we exploited a strategy to create a novel chimeric molecule (named drosotoxin) with high selectivity for channel subtypes, which was achieved by using drosomycin to substitute the structural core of BmKITc, a depressant toxin acting on both insect and mammalian Na+ channels. Recombinant drosotoxin selectively inhibited tetrodotoxin-resistant (TTX-R) Na+ channels in rat dorsal root ganglion (DRG) neurons with a 50% inhibitory concentration (IC50) of 2.6 +/- 0.5 mu M. This chimeric peptide showed no activity on K+, Ca2+ and TTX-sensitive (TTX-S) Na+ channels in rat DRG neurons and Drosophila para/tipE channels at micromolar concentrations. Drosotoxin represents the first chimeric toxin and example of a non-toxic core scaffold with high selectivity on mammalian TTX-R Na+ channels. (C) 2010 Elsevier Inc. All rights reserved.
ISSN: 0006-2952
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
× corresponding author
# (joint) last author

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