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

Authors

Adam C. Kennedy, Alessia Belgi, Benjamin W. Husselbee, David Spanswick, Ray S. Norton, Andrea J. Robinson

Published Toxins
Graphical abstract  
Abstract

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

Citation

A. C. Kennedy, A. Belgi, B. W. Husselbee, D. Spanswick, R. S. Norton, A. J. Robinson, “α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia”, Toxins, 2020, 12(8), 505

Pdf  
Doi

https://doi.org/10.3390/toxins12080505

Keywords conotoxins; peptides; analgesia; disulfide; dicarba peptides; GABAB; nAChR.

This entry was posted in Conotoxins, Publications 2020. Bookmark the permalink.

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