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Transport of phosphorylated compounds across lipid bilayers by supramolecular receptors

Project description

Synthetic receptors for transporting nucleotides across biological membranes

Cells are surrounded by biological membranes which serve as barriers from the surrounding environment but also facilitate communication, enabling for example the selective transport of molecules. Ion transport in cells does not take place passively but is carried out by dedicated ion transporter proteins that span the cell membrane. The key objective of the EU-funded ORGANITRA project is to develop synthetic receptors that can transport phosphate and phosphorylated compounds such as nucleotides across membranes. Using scaffolds and combinatorial chemistry, researchers will generate synthetic receptors that can be employed to selectively introduce nucleotides into liposomes and cells. ORGANITRA deliverables will open new possibilities in biochemistry and biotechnology fields.

Objective

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.

Host institution

UNIVERSITE LIBRE DE BRUXELLES
Net EU contribution
€ 1 485 274,00
Address
AVENUE FRANKLIN ROOSEVELT 50
1050 Bruxelles / Brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 485 274,00

Beneficiaries (1)