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Muestra selección de péptidos macrocíclicos exóticos expresados bajo un código genético de 23 aminoácidos
Toby Passioura1, Wenyu Liu1, Daniel Dunkelmann1
1Department of Chemistry , Graduate School of Science, The University of Tokyo , 7-3-1, Hongo , Tokyo 113-0033 , Japan.
Journal of the American Chemical Society
|August 30, 2018
Resumen
Los investigadores crearon nuevos péptidos macrocíclicos hidrofóbicos utilizando un código genético reprogramado. Este método identificó con éxito ligandos de alta afinidad para el receptor de interleucina-6 (IL6R), ampliando las posibilidades de descubrimiento de fármacos peptídicos.
Área de la Ciencia:
- La bioquímica
- Biología molecular
- Biología sintética
Sus antecedentes:
- Los péptidos macrocíclicos que se producen naturalmente a menudo muestran una preferencia por los residuos de aminoácidos hidrofóbicos.
- Las tecnologías de visualización in vitro permiten el descubrimiento de los ligandos peptídicos macrocíclicos para proteínas específicas.
- Los métodos actuales se limitan a las bibliotecas de péptidos que utilizan el código genético estándar, mezclando aminoácidos hidrofóbicos e hidrofílicos.
Objetivo del estudio:
- Para demostrar la expresión ribosómica de péptidos macrocíclicos exóticos utilizando un código genético hidrofóbico reprogramado.
- Validar la viabilidad de este enfoque para el descubrimiento de nuevos ligandos peptídicos.
- Identificar los ligandos peptídicos macrocíclicos de alta afinidad para el receptor de la interleucina-6 (IL6R).
Principales métodos:
- Desarrollo de un código genético radicalmente reprogramado que incorpora 12 aminoácidos proteinogénicos y 11 no proteinogénicos.
- Construcción y selección de una biblioteca de péptidos basada en este código genético hidrofóbico.
- Estudio de caso que incluye el cribado de afinidad con el receptor de la interleucina-6 (IL6R).
Principales resultados:
- Expresión ribosómica exitosa de péptidos macrocíclicos exóticos utilizando el código genético reprogramado.
- Identificación de los exóticos peptídicos macrocíclicos con una alta afinidad por IL6R.
- Validación del enfoque para el descubrimiento de ligandos de péptidos macrocíclicos exóticos relativamente hidrofóbicos.
Conclusiones:
- El estudio valida un nuevo enfoque para generar y descubrir péptidos macrocíclicos exóticos relativamente hidrofóbicos.
- Este método expande el alcance de la composición de la biblioteca de péptidos más allá del código genético estándar.
- Los hallazgos apoyan el potencial de esta técnica para identificar potentes ligandos de péptidos para objetivos terapéuticos como IL6R.
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