α-Conotoxin Peptidomimetics: Probing the Minimal Binding Motif for Effective Analgesia.
Toxins (Basel)
; 12(8)2020 08 06.
Article
em En
| MEDLINE
| ID: mdl-32781580
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Conotoxinas
/
Peptidomiméticos
/
Analgésicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Toxins (Basel)
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Austrália