De novo synthesis of modified saxitoxins for sodium ion channel study.
J Am Chem Soc
; 131(35): 12524-5, 2009 Sep 09.
Article
en En
| MEDLINE
| ID: mdl-19678702
ABSTRACT
Access to novel forms of (+)-saxitoxin (STX), a potent and selective inhibitor of voltage-gated Na(+) ion channels, has been made possible through de novo synthesis. Saxitoxin is believed to lodge in the outer mouth of the channel pore, thereby stoppering ion flux. Herein, we demonstrate that modification of the C13-carbamoyl unit can be accommodated in the binding site of the protein without significantly reducing ligand-receptor affinity. These discoveries have emboldened efforts to prepare photoaffinity-labeled and other unique forms of STX as pharmacological tools for interrogating both the molecular architecture and function of Na(+) channels. A synthetic plan that makes such compounds generally available is described.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Saxitoxina
/
Canales de Sodio
/
Bloqueadores de los Canales de Sodio
Límite:
Animals
Idioma:
En
Revista:
J Am Chem Soc
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos