Stabilization of α-conotoxin AuIB: Influences of disulfide connectivity and backbone cyclization

Lovelace, Erica S., Gunasekera, Sunithi, Alvarmo, Charlotta, Clark, Richard J., Nevin, Simon T., Grishin, Anton A., Adams, David J., Craik, David J. and Daly, Norelle L. (2011) Stabilization of α-conotoxin AuIB: Influences of disulfide connectivity and backbone cyclization. Antioxidants and Redox Signaling, 14 1: 87-95. doi:10.1089/ars.2009.3068

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Author Lovelace, Erica S.
Gunasekera, Sunithi
Alvarmo, Charlotta
Clark, Richard J.
Nevin, Simon T.
Grishin, Anton A.
Adams, David J.
Craik, David J.
Daly, Norelle L.
Title Stabilization of α-conotoxin AuIB: Influences of disulfide connectivity and backbone cyclization
Journal name Antioxidants and Redox Signaling   Check publisher's open access policy
ISSN 1523-0864
Publication date 2011-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1089/ars.2009.3068
Open Access Status File (Author Post-print)
Volume 14
Issue 1
Start page 87
End page 95
Total pages 9
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Collection year 2011
Language eng
Formatted abstract
α-Conotoxins are peptides isolated from the venom ducts of cone snails that target nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential applications for treating a range of conditions in humans, including pain. However, like all peptides, conotoxins are susceptible to degradation, and to enhance their therapeutic potential it is important to elucidate the factors contributing to instability and to develop approaches for improving stability. AuIB is a unique member of the α-conotoxin family because the nonnative "ribbon" disulfide isomer exhibits enhanced activity at the nAChR in rat parasympathetic neurons compared with the native "globular" isomer. Here we show that the ribbon isomer of AuIB is also more resistant to disulfide scrambling, despite having a nonnative connectivity and flexible structure. This resistance to disulfide scrambling does not correlate with overall stability in serum because the ribbon isomer is degraded in human serum more rapidly than the globular isomer. Cyclization via the joining of the N- and C-termini with peptide linkers of four to seven amino acids prevented degradation of the ribbon isomer in serum and stabilized the globular isomers to disulfide scrambling. The linker length used for cyclization strongly affected the relative proportions of the disulfide isomers produced by oxidative folding. Overall, the results of this study provide important insights into factors influencing the stability and oxidative folding of α-conotoxin AuIB and might be valuable in the design of more stable antagonists of nAChRs.
Keyword Disulfide
Alpha conotoxin AuIB
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Online Ahead of Print: August 20, 2010. Fulltext open access - this is a copy of an article published in the Antioxidants and Redox Signaling © 2011 [copyright Mary Ann Liebert, Inc.]; Antioxidants and Redox Signaling is available online at:

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 24 Oct 2010, 00:09:43 EST