Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3.

Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3.

Jensen, J, Durek, T, Alewood, P, Adams, DJ, King, G and Rash, L 2009, 'Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3.', Toxicon, vol. 54, no. 1, pp. 56-61.

Document type:	Journal Article
Collection:	Journal Articles

Title	Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3.
Author(s)	Jensen, J Durek, T Alewood, P Adams, DJ King, G Rash, L
Year	2009
Journal name	Toxicon
Volume number	54
Issue number	1
Start page	56
End page	61
Total pages	5
Publisher	Pergamon
Abstract	Acid sensing ion channels (ASICs) are pH-sensitive channels that are distributed in the central and peripheral nervous system and which are believed to play a key role in pain perception. APETx2, a 42-residue peptide toxin isolated from the sea anemone Anthopleura elegantissima, is the only known selective inhibitor of ASIC3 channels. Here we describe the total chemical synthesis of APETx2 by solid-phase peptide synthesis and native chemical ligation. The folded synthetic toxin had an IC50 of 57 nM for inhibition of rat ASIC3 channels expressed in Xenopus oocytes, in agreement with the IC50 reported for the native toxin (63 nM). The native chemical ligation approach should provide an efficient route for synthesis of other pharmacologically useful disulfide-rich toxins from venomous animals.
Subject	Basic Pharmacology
Keyword(s)	APETx2 acid sensing ion channel solid-phase peptide synthesis native chemical ligation disulfide bond protein folding
Copyright notice	© 2009 Elsevier
ISSN	0041-0101

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