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

ABSTRACT: Several analgesic ?-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 ?-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 ?-conotoxins at each of these targets has hampered the development of therapeutic leads. This review scrutinises the N-terminal domain of the ?-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.

SUBMITTER: Kennedy AC 

PROVIDER: S-EPMC7472027 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature