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Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging
Published on: July 21, 2011
Agentes de contraste de resonancia magnética con proteínas sustituidas por metales diseñados para mejorar la
Victor S Lelyveld1, Eric Brustad, Frances H Arnold
1Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|December 22, 2010
Resumen
Los investigadores mejoraron los agentes de contraste de resonancia magnética (IRM) mediante la creación de metaloproteínas que contienen manganeso. Estas proteínas diseñadas muestran una mejor relaxividad de protones, lo que permite imágenes moleculares más sensibles para las vías de señalización biológica.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- La biofísica es la biofísica.
Sus antecedentes:
- Las metaloproteínas de ingeniería están surgiendo como agentes de imagen molecular sensibles al analito para imágenes de resonancia magnética (IRM).
- Los agentes de contraste de metaloproteína actuales a menudo exhiben efectos más débiles en comparación con las alternativas sintéticas.
- La mejora de la relaxividad de protones es clave para mejorar la sensibilidad de estos agentes basados en proteínas.
Objetivo del estudio:
- Para aumentar la relaxividad de protones de los agentes de contraste de resonancia magnética de metaloproteína de ingeniería derivados del citocromo P450 BM3 dominio hemo (BM3h).
- Desarrollar un sensor de resonancia magnética robusto basado en proteínas con una sensibilidad significativa al ligando para aplicaciones biológicas.
Principales métodos:
- Sustitución de metales: sustitución de hierro férrico nativo por manganeso (III) en las variantes BM3h para aumentar el espín de los electrones.
- Ingeniería de proteínas: coexpresar variantes de BM3h con el transportador de hemo bacteriano ChuA en E. coli.
- Incorporación de ligando: complementando el medio de crecimiento con Mn3+-protoporfirina IX para la incorporación de manganeso.
- Medidas de relaxividad: evaluación de las relaxividades T1 de las variantes BM3h de ingeniería a 4.7 T.
Principales resultados:
- Las variantes mangánicas de BM3h demostraron hasta 2.6 veces más relaxividades T1 en comparación con las BM3h nativas.
- La sustitución por porfirina mediada por ChuA produjo un derivado BM3h estable y de alta relaxividad.
- El derivado BM3h diseñado mostró un cambio del 63% en la relaxividad tras la unión del ácido araquidónico.
Conclusiones:
- La sustitución de metales, específicamente utilizando manganeso, es una estrategia efectiva para mejorar la relaxividad de protones de los agentes de resonancia magnética de metaloproteína diseñados.
- Los sensores de resonancia magnética basados en proteínas con alta sensibilidad al ligando se pueden desarrollar fácilmente utilizando técnicas de sustitución de metales.
- Este enfoque ofrece un método flexible para crear agentes avanzados de imagen molecular para el estudio de las vías de señalización biológica.
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