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Los ligandos G-cuadruplex de péptidos ciclicos seleccionados por afinidad imitan un mecanismo de unión similar al de

Kim C Liu¹, Konstantin Röder¹, Clemens Mayer^1,2

¹Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, U.K.

Journal of the American Chemical Society

|April 9, 2020

Resumen

Los investigadores desarrollaron nuevos péptidos bicíclicos que se unen a los cuádruplexos G (G4), ofreciendo una nueva forma de controlar la expresión génica apuntando a las estructuras de ácido nucleico.

Área de la Ciencia:

La bioquímica
Biología molecular
Química medicinal

Sus antecedentes:

Los G-cuadruplexos (G4s) son estructuras de ácido nucleico vinculadas a la expresión génica y la replicación del ADN.
Dirigirse a las estructuras G4 con ligandos ofrece un método para modular la expresión génica.

Objetivo del estudio:

Para explorar los péptidos cíclicos como una nueva clase de ligandos G4.
Desarrollar y caracterizar de novo los péptidos bicíclicos que se unen al G4.

Principales métodos:

Muestra de fagos para la selección de péptidos cíclicos.
Ensayos biofísicos para determinar la afinidad y la selectividad de la unión.
Simulaciones moleculares para elucidar los mecanismos de unión.

Principales resultados:

Los péptidos bicíclicos seleccionados muestran una afinidad submicromolar por las estructuras G4.
Estos péptidos demuestran una alta selectividad para los G4 sobre el ADN de doble hélice.
Las simulaciones moleculares confirman las fortalezas de unión y revelan mecanismos específicos de reconocimiento de G4.

Conclusiones:

Los péptidos bicíclicos representan una nueva clase prometedora de ligandos G4.
Este enfoque expande el espacio químico para apuntar a las estructuras de ácido nucleico.
Los hallazgos proporcionan información sobre el reconocimiento de G4 por parte de los ligandos peptídicos.

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