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From light-stimulated anion receptors to transmembrane carriers and pumps

Descripción del proyecto

Síntesis de transportadores transmembrana de aniones activados por luz

El transporte de aniones por la membrana celular es fundamental para muchos procesos biológicos. El programa de investigación financiado con fondos europeos LIGHTPORT tiene por objeto crear un sistema artificial con receptores aniónicos en el que las propiedades de enlace puedan modularse mediante luz y que se puedan utilizar como portadores transmembrana para regular el transporte pasivo e inducir el activo. Los objetivos del programa incluyen la creación de fotoconmutadores accionados por luz visible, la producción de estructuras entrelazadas de forma mecánica como hospedadores fotoconmutables, la aplicación de estas estructuras para el transporte controlado por luz y el bombeo impulsado por luz de aniones por las bicapas fosfolipídicas. El objetivo general es utilizar este trabajo para establecer tratamientos farmacológicos localizados basados en la luz, como la eliminación activada por luz de células cancerígenas o bacterianas.

Objetivo

The transport of anions across the cell membrane, which is mediated by transport proteins, is essential to many important biological processes. Dysregulation of this transport has been associated to various diseases and therefore, chemists endeavour to develop artificial receptors that mimic the function of natural transporters. Despite much progress over the last decade, the current artificial systems are mostly static, while proteins are able to change their activity dynamically in response to stimuli in the environment. To integrate such stimuli-controlled behavior in synthetic systems is a key contemporary challenge. In view of this, the goal of the proposed research program is to develop anion receptors in which the binding properties can be effectively modulated by light and to apply these receptors as transmembrane carriers and pumps, in order to regulate passive transport (i.e. down a concentration gradient) and to induce active transport (i.e. against a concentration gradient). This interdisciplinary program is divided into three work packages: WP1 aims at the development of structurally rigid and visible-light-actuated photoswitches and their use as platforms for constructing anion receptors; WP2 deals with the development of mechanically interlocked structures as photoswitchable anionic hosts; WP3 is directed at utilizing these receptors for light-gated transport and light-driven pumping of anions across phospholipid bilayers, whereas also an alternative dual-responsive anion channel will be prepared. Eventually, it is expected that this work will open a new route toward light-based localized pharmacological treatment, e.g. via light-triggered cancer or bacterial cell death. Furthermore, active transport systems, that are able to build up and maintain concentration gradients across membranes, could provide a completely new view on how to convert and store light (solar) energy.

Régimen de financiación

ERC-STG - Starting Grant

Institución de acogida

UNIVERSITEIT LEIDEN
Aportación neta de la UEn
€ 1 499 461,00
Dirección
RAPENBURG 70
2311 EZ Leiden
Países Bajos

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Región
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 499 461,00

Beneficiarios (2)