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Review

α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia

1
School of Chemistry, Monash University, Clayton, Victoria 3800, Australia
2
Biomedicine Discovery Institute and the Department of Physiology, Monash University, Victoria 3800, Australia
3
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
4
NeuroSolutions Ltd., Coventry CV4 7AL, UK
5
Medicinal Chemistry, Monash Institute of Pharmaceutical Science, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia
6
ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript and share first authorship.
Toxins 2020, 12(8), 505; https://doi.org/10.3390/toxins12080505
Received: 24 June 2020 / Revised: 29 July 2020 / Accepted: 3 August 2020 / Published: 6 August 2020
(This article belongs to the Special Issue Conotoxins: Characterization, Pharmacology, and Therapeutics)
Several analgesic α-conotoxins have been isolated from marine cone snails. Structural modification of native peptides has provided potent and selective analogues for two of its known biological targets—nicotinic acetylcholine and γ-aminobutyric acid (GABA) G protein-coupled (GABAB) receptors. Both of these molecular targets are implicated in pain pathways. Despite their small size, an incomplete understanding of the structure-activity relationship of α-conotoxins at each of these targets has hampered the development of therapeutic leads. This review scrutinises the N-terminal domain of the α-conotoxin family of peptides, a region defined by an invariant disulfide bridge, a turn-inducing proline residue and multiple polar sidechain residues, and focusses on structural features that provide analgesia through inhibition of high-voltage-activated Ca2+ channels. Elucidating the bioactive conformation of this region of these peptides may hold the key to discovering potent drugs for the unmet management of debilitating chronic pain associated with a wide range of medical conditions. View Full-Text
Keywords: conotoxins; peptides; analgesia; disulfide; dicarba peptides; GABAB; nAChR. conotoxins; peptides; analgesia; disulfide; dicarba peptides; GABAB; nAChR.
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MDPI and ACS Style

Kennedy, A.C.; Belgi, A.; Husselbee, B.W.; Spanswick, D.; Norton, R.S.; Robinson, A.J. α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia. Toxins 2020, 12, 505. https://doi.org/10.3390/toxins12080505

AMA Style

Kennedy AC, Belgi A, Husselbee BW, Spanswick D, Norton RS, Robinson AJ. α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia. Toxins. 2020; 12(8):505. https://doi.org/10.3390/toxins12080505

Chicago/Turabian Style

Kennedy, Adam C., Alessia Belgi, Benjamin W. Husselbee, David Spanswick, Raymond S. Norton, and Andrea J. Robinson. 2020. "α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia" Toxins 12, no. 8: 505. https://doi.org/10.3390/toxins12080505

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