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Construcción de una biblioteca de péptidos miméticos de proteínas secuenciables con un verdadero espacio químico

Zhonghan Li¹, Shiqun Shao¹, Xiaodong Ren¹

¹Department of Chemistry , University of California, Riverside , Riverside , California 92521 , United States.

Journal of the American Chemical Society

|October 27, 2018

Resumen

Desarrollamos nuevos péptidos bicíclicos que imitan las proteínas. Un péptido se dirige a la oncoproteína c-Myc, inhibiendo la proliferación de las células cancerosas al interferir con la transcripción.

Área de la Ciencia:

Química medicinal
Biología molecular
Biotecnología

Sus antecedentes:

Las proteínas intrínsecamente desordenadas como c-Myc son objetivos terapéuticos desafiantes.
Los imitadores de proteínas ofrecen una alternativa prometedora a las drogas tradicionales.

Objetivo del estudio:

Para crear una biblioteca de nuevos péptidos bicíclicos con un espacio químico diverso.
Para identificar y caracterizar un péptido que inhibe la actividad de c-Myc.

Principales métodos:

Síntesis de péptidos bicíclicos mediante la química de clic y la metátesis de cierre de anillo.
Secuenciación de péptidos a través de la degradación de Edman y espectrometría de masas después de la linearización.
Cribado de alto rendimiento contra el epitopo c-Myc E363-R378.
Pruebas in vitro de la eficacia del péptido en líneas celulares de glioblastoma.

Principales resultados:

Se sintetizó una biblioteca de péptidos bicíclicos rígidos de tamaño nanométrico con cadenas laterales espacialmente diversas.
Se identificó un péptido específico que se une a la oncoproteína c-Myc.
Este péptido demostró una administración intracelular, interfirió con la transcripción mediada por c-Myc e inhibió la proliferación celular del glioblastoma.

Conclusiones:

Los péptidos bicíclicos representan un andamio versátil para el desarrollo de nuevas terapias.
La orientación de c-Myc con inhibidores específicos de péptidos muestra potencial para el tratamiento del glioblastoma.

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