کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2513309 | 1118405 | 2010 | 7 صفحه PDF | دانلود رایگان |

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 μM. 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.
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Journal: Biochemical Pharmacology - Volume 80, Issue 8, 15 October 2010, Pages 1296–1302