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Transport of phosphorylated compounds across lipid bilayers by supramolecular receptors

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.

Call for proposal

ERC-2018-STG
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Host institution

UNIVERSITE LIBRE DE BRUXELLES
Address
Avenue Franklin Roosevelt 50
1050 Bruxelles
Belgium
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 485 274

Beneficiaries (1)

UNIVERSITE LIBRE DE BRUXELLES
Belgium
EU contribution
€ 1 485 274
Address
Avenue Franklin Roosevelt 50
1050 Bruxelles
Activity type
Higher or Secondary Education Establishments