Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3

Bioorg Med Chem. 2019 Jan 1;27(1):247-253. doi: 10.1016/j.bmc.2018.12.009. Epub 2018 Dec 6.

Abstract

The scorpion toxin AmmTx3 is a specific blocker of Kv4 channels. It was shown to have interesting potential for neurological disorders. In this study, we report the first chemical synthesis of AmmTx3 by using the native chemical ligation strategy and validate its biological activity. We determined its 3D structure by nuclear magnetic resonance spectroscopy, and pointed out that AmmTx3 possesses the well-known CSαβ structural motif, which is found in a large number of scorpion toxins. Overall, this study establishes an easy synthetic access to biologically active AmmTx3 toxin.

Keywords: AmmTx3; NMR; Native chemical ligation; Potassium channel; Toxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cerebellum / drug effects
  • Mice, Inbred C57BL
  • Neurons / drug effects
  • Potassium Channel Blockers / chemical synthesis
  • Potassium Channel Blockers / chemistry*
  • Potassium Channel Blockers / pharmacology
  • Protein Conformation, alpha-Helical
  • Scorpion Venoms / chemical synthesis
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / pharmacology
  • Scorpions / chemistry

Substances

  • AmmTX3 protein, Androctonus mauretanicus
  • Potassium Channel Blockers
  • Scorpion Venoms