Skip to main content
European Commission logo print header

Transport of phosphorylated compounds across lipid bilayers by supramolecular receptors

Descripción del proyecto

Receptores sintéticos para el transporte de nucleótidos a través de las membranas biológicas

Las células están rodeadas por membranas biológicas que sirven de barrera frente al entorno, pero que también facilitan la comunicación al permitir, por ejemplo, el transporte selectivo de moléculas. El transporte de iones a las células no se produce de forma pasiva, sino que lo llevan a cabo proteínas transportadoras de iones específicas que atraviesan la membrana celular. El objetivo principal del proyecto ORGANITRA, financiado con fondos europeos, es desarrollar receptores sintéticos que puedan transportar fosfatos y compuestos fosforilados, como los nucleótidos, a través de las membranas. Gracias a las estructuras y la química combinatoria, los investigadores generarán receptores sintéticos que pueden emplearse para introducir nucleótidos en liposomas y células de forma selectiva. Los resultados de ORGANITRA abrirán nuevas posibilidades en los campos de la bioquímica y la biotecnología.

Objetivo

This ORGANITRA project addresses transmembrane transport. Lipid bilayer membranes not only define the borders of cells and their compartments but are also implicated in metabolic processes and signal transduction. Membranes function as impermeable barriers for ionic and hydrophilic species which can only cross the membrane with the aid of dedicated membrane proteins.
For biotechnological and biophysical applications, the development of anion carriers that can bind an anion and transport it across the lipid bilayer could be of great relevance. In this project, synthetic anion receptors will be developed to bind biologically relevant organic phosphorylated compounds, like nucleotides. These receptors will then be used to transport these organophosphates across membranes.
The receptors will be synthesised by dynamic combinatorial chemistry. Building blocks containing urea or thiourea groups, for efficient phosphate binding, will be connected to multi-armed scaffolds by hydrazone groups. The dynamic character of these bonds will be used to identify efficient receptors from libraries of compounds, using different phosphorylated compounds as templates. With this approach, selective receptors for different nucleotides and related compounds can be obtained.
The transport performance of the receptors will be evaluated with newly developed assays. Liposomes will be used as model systems and transport will be monitored by fluorescence spectroscopy using the quenching of the emission of an encapsulated phosphate sensitive dye. Additionally, the mechanism of the transport processes will be elucidated by fluorescence and 1H and 31P NMR spectroscopies.
Transmembrane carriers for phosphorylated compounds will make it possible to selectively introduce nucleotides into liposomes and cells, opening the way to fuel enzymes with adenosine triphosphate (ATP) in liposomes as biotechnological nanoreactors and to study nucleotide-dependent biochemical processes in cells.

Régimen de financiación

ERC-STG - Starting Grant

Institución de acogida

UNIVERSITE LIBRE DE BRUXELLES
Aportación neta de la UEn
€ 1 485 274,00
Dirección
AVENUE FRANKLIN ROOSEVELT 50
1050 Bruxelles / Brussel
Bélgica

Ver en el mapa

Región
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 485 274,00

Beneficiarios (1)