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

Jensen, J. E., Durek, T, Alewood, P. F., Adams, D. J., King, G. F. and Rash, L. D. (2009) Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3. TOXICON, 54 1: 56-61. doi:10.1016/j.toxicon.2009.03.014


Author Jensen, J. E.
Durek, T
Alewood, P. F.
Adams, D. J.
King, G. F.
Rash, L. D.
Title Chemical synthesis and folding of APETx2, a potent and selective inhibitor of acid sensing ion channel 3
Journal name TOXICON   Check publisher's open access policy
ISSN 0041-0101
Publication date 2009-07-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.toxicon.2009.03.014
Open Access Status DOI
Volume 54
Issue 1
Start page 56
End page 61
Total pages 6
Editor Alan L. Harvey
Place of publication Oxford, England, U.K.
Publisher Pergamon
Language eng
Subject C1
970103 Expanding Knowledge in the Chemical Sciences
0304 Medicinal and Biomolecular Chemistry
030406 Proteins and Peptides
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.
Keyword APETx2
Inflammatory pain
Acid sensing ion channel
Solid-phase peptide synthesis
Native chemical ligation
Disulfide bond
Protein folding
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 511067
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 03 Sep 2009, 17:58:12 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience