Facile and efficient chemical synthesis of APET×2, an ASIC-targeting toxin, via hydrazide-based native chemical ligation

Acid-sensing ion channels (ASICs) targeting peptides APET×2, a minor constituent in the venom of the sea anemone Anthopleura elegantissima, was synthesized via hydrazide-based native chemical ligation with high yields. Synthetic APET×2 exhibited well-defined three-dimensional structure after an optimized folding process. Therefore, we present a simple and cost-efficient strategy for the chemical synthesis of ASIC3 inhibitor APET×2.