Characterization of a novel alpha-conotoxin TxID from Conus textile that potently blocks rat alpha3/beta4 nicotinic acetylcholine receptors

Luo, Sulan, Zhangsun, Dongting, Zhu, Xiaopeng, Wu, Yong, Hu, Yuanyan, Christensen, Sean, Harvey, Peta J., Akcan, Muharrem, Craik, David J. and McIntosh, Michael (2013) Characterization of a novel alpha-conotoxin TxID from Conus textile that potently blocks rat alpha3/beta4 nicotinic acetylcholine receptors. Journal of Medicinal Chemistry, Article ASAP A-I. doi:10.1021/jm401254c

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Author Luo, Sulan
Zhangsun, Dongting
Zhu, Xiaopeng
Wu, Yong
Hu, Yuanyan
Christensen, Sean
Harvey, Peta J.
Akcan, Muharrem
Craik, David J.
McIntosh, Michael
Title Characterization of a novel alpha-conotoxin TxID from Conus textile that potently blocks rat alpha3/beta4 nicotinic acetylcholine receptors
Formatted title
Characterization of a novel α‑conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 2013-11-07
Sub-type Article (original research)
DOI 10.1021/jm401254c
Open Access Status File (Author Post-print)
Volume Article ASAP
Start page A
End page I
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2014
Language eng
Formatted abstract
The α3β4 nAChRs are implicated in pain sensation in the PNS and addiction to nicotine in the CNS. We identified an α-4/ 6-conotoxin (CTx) TxID from Conus textile. The new toxin consists of 15 amino acid residues with two disulfide bonds. TxID was synthesized using solid phase methods, and the synthetic peptide was functionally tested on nAChRs heterologously expressed in Xenopus laevis oocytes. TxID blocked rat α3β4 nAChRs with a 12.5 nM IC50, which places it among the most potent α3β4 nAChR antagonists. TxID also blocked the closely related α6/α3β4 with a 94 nM IC50 but showed little activity on other nAChR subtypes. NMR analysis showed that two major structural isomers exist in solution, one of which adopts a regular α-CTx fold but with different surface charge distribution to other 4/6 family members. α-CTx TxID is a novel tool with which to probe the structure and function of α3β4 nAChRs.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 10 Dec 2013, 12:01:53 EST by Susan Allen on behalf of Institute for Molecular Bioscience