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Foldamer heterogéneo de la estructura terciaria del dedo de zinc
Kelly L George1, W Seth Horne1
1Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
Journal of the American Chemical Society
|May 17, 2017
Resumen
Los investigadores crearon nuevos foldamers con columnas vertebrales modificadas que imitan las estructuras naturales de las proteínas. Estas moléculas diseñadas demuestran una mayor estabilidad y pliegues nativos, ampliando las posibilidades de diseño biomimético.
Área de la Ciencia:
- La bioquímica
- Biología Química
- Biología estructural
Sus antecedentes:
- Los foldameros son oligómeros artificiales con diversas aplicaciones, capaces de adoptar estructuras definidas.
- Mientras que las estructuras secundarias como las hélices y las láminas son alcanzables con columnas vertebrales no naturales, los pliegues terciarios son menos comunes.
- Los foldameres de espina dorsal heterogéneos, alterando las secuencias naturales de proteínas, ofrecen un camino hacia pliegues complejos, pero a menudo enfrentan desafíos de estabilidad.
Objetivo del estudio:
- Diseñar y caracterizar los foldameres de espina dorsal heterogéneos que imitan la estructura terciaria de los dominios del dedo de zinc.
- Investigar si las modificaciones de la columna vertebral pueden mejorar la estabilidad del pliegue en comparación con los prototipos de proteínas naturales.
- Ampliar los principios de diseño de los foldamers para incluir estructuras terciarias complejas.
Principales métodos:
- Alteración sistemática de la columna vertebral de las secuencias de proteínas naturales para mostrar cadenas laterales nativas en bloques de construcción no naturales.
- Utilizando espectroscopia UV-vis, calorimetría de titulación isotérmica y RMN multidimensional para analizar la estructura y la estabilidad del pliegue.
- Diseño de oligómeros con más del 20% de columna vertebral modificada para evaluar las propiedades estructurales y termodinámicas.
Principales resultados:
- Creado con éxito foldamers heterogéneos de columna vertebral que imitan el motivo terciario del dedo de zinc.
- Se demostró que estos foldamers poseen una mayor estabilidad termodinámica en comparación con sus contrapartes de proteínas naturales.
- Se han confirmado pliegues terciarios nativos y entornos de unión de metales a través de la caracterización biofísica.
Conclusiones:
- La modificación juiciosa de la columna vertebral en el diseño del pliegue puede conducir a una mayor estabilidad del pliegue.
- Los foldameres de espina dorsal heterogénea pueden imitar con éxito estructuras terciarias complejas como los dominios del dedo de zinc.
- Este trabajo expande la utilidad de los foldamers a nuevas clases estructurales y demuestra una mejor estabilidad biomimética.
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