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Updated: Apr 27, 2026

Examining Monosynaptic Connections in Drosophila Using Tetrodotoxin Resistant Sodium Channels
Published on: February 14, 2018
Studies examining the relationship between the chemical structure of protoxin II and its activity on voltage gated
Jae H Park1, Kevin P Carlin, Gang Wu
1Discovery Research, Purdue Pharma L.P. , 6 Cedar Brook Drive, Cranbury, New Jersey 08512, United States.
Abstract:
The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a well-defined inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region, similar to previously described NaSpTx III tarantula toxins. In the present study we sought to explore the structure-activity relationship of the two regions of the ProTx II molecule. As a first step, chimeric toxins of ProTx II and PaTx I were synthesized and their biological activities on Nav1.7 and Nav1.2 channels were investigated. Other tail region modifications to this chimera explored the effects of tail length and tertiary structure on sodium channel activity. In addition, the activity of various C-terminal modifications of the native ProTx II was assayed and resulted in the identification of protoxin II-NHCH3, a molecule with greater potency against Nav1.7 channels (IC50=42 pM) than the original ProTx II.
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