Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for potency, selectivity, and half-life.
J Biol Chem
; 289(33): 22704-22714, 2014 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-24939846
ABSTRACT
Ion channels are an attractive class of drug targets, but progress in developing inhibitors for therapeutic use has been limited largely due to challenges in identifying subtype selective small molecules. Animal venoms provide an alternative source of ion channel modulators, and the venoms of several species, such as scorpions, spiders and snails, are known to be rich sources of ion channel modulating peptides. Importantly, these peptides often bind to hyper-variable extracellular loops, creating the potential for subtype selectivity rarely achieved with small molecules. We have engineered scorpion venom peptides and incorporated them in fusion proteins to generate highly potent and selective Kv1.3 inhibitors with long in vivo half-lives. Kv1.3 has been reported to play a role in human T cell activation, and therefore, these Kv1.3 inhibitor fusion proteins may have potential for the treatment of autoimmune diseases. Our results support an emerging approach to generating subtype selective therapeutic ion channel inhibitors.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
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Venenos de Escorpión
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Activación de Linfocitos
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Linfocitos T
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Ingeniería de Proteínas
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Bloqueadores de los Canales de Potasio
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Canal de Potasio Kv1.3
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Proteínas de Artrópodos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article