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Helical foldamers with tunable channels for transmembrane water and ion transport

Project description

Improved synthetic structures to mimic biological ion and water channels

In higher organisms, cells are surrounded by membranes that separate them from the external environment and mediate the exchange of fluids, electrolytes or proteins. These membranes are typically composed of proteins that act like channels that open and close in response to selective ions and molecules. Research has largely focused on engineered biological ion channels to further understand their mechanism and how they could potentially treat certain diseases, such as channelopathies. Funded by the Marie Skłodowska-Curie Actions programme, the HeliTrans project plans to synthesise the first unimolecular synthetic ion or water channel. The project will build on earlier achievements in aromatic foldamer design to improve the selectivity of the synthetic ion and water channels.

Objective

The development of synthetic molecules capable of mimicking the modes of action of biological ion and water membrane channels is crucial to understand their mechanism and potentially to cure diseases (channelopathies) associated with their malfunctions. Synthetic transporters and channels that have already been reported so far, suffer from ill-defined structures or complex mechanisms that make it difficult to establish structure-property relationships in order to improve their efficiency and selectivity. This project aims at designing, synthesizing and studying the very first membrane spanning unimolecular synthetic ion or water channels in the form of long helically folded aromatic oligomers with suitably oriented binding sites at the inner rim. It builds upon earlier achievements in aromatic foldamer design concerning both molecular recognition in helical cavities, and the development of efficient solid phase synthetic methods (SPS) to access sequences longer than 40 units. About 40 units are predicted to fold in a 10-turn open-ended helix with a sizeable channel, covering a total height of ~35 Å, which is equivalent to the thickness of a lipid membrane. Such objects would be structurally stable and well-defined, amenable to structural fine-tuning by changing the composition of individual monomers one at a time, to modulate channel diameter and polar/apolar features. Their channeling behavior will be studied in vesicles and planar bilayers and will be correlated to their structure. Such correlation will allow, for the first time in the field, to build predictive design capabilities. This multidisciplinary project will enrich my strong background on artificial membrane channels with foldamer chemistry and should be decisive to help me reaching an independent academic research position.

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Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution
€ 174 806,40
Address
Geschwister scholl platz 1
80539 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00