HeliTrans · Helical foldamers with tunable channels for transmembrane water and ion transport
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2022-06-01 → 2024-05-31
- EU contribution
- €174,806
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Helical foldamers with tunable channels for transmembrane water and ion transport
Ion and water transport across cell membranes is an essential biological phenomenon involved in the maintenance of cell volume, the regulation of cellular pH and in signalling pathways. Abnormalities in ion transport causes several diseases, namely, channelopathies, e.g., myotonia, nephrolithiasis, Bartter’s syndrome, osteoporosis. In order to explore the functions and modes of action of the biological ion channels, studying them directly is of particular relevance. However, most of them are complex protein structures, difficult to produce, manipulate and modulate. The development of synthetic ion transporters as mimics of their natural congeners is thus an important complementary area of fundamental research. In this context, our MSCA-IF project, HeliTrans aims at the design, synthesis and study of the very first active and selective membrane spanning unimolecular synthetic channels in the form of long helically folded aromatic oligomers with suitably oriented binding sites. Apart from the fact that the development of synthetic ion transporters have potential to function as mimic of their natural congeners, selective transporters could find medical applications through channel replacement therapy, e.g. for Cystic Fibrosis. With another focus, selective water transporters may inspire new generations of water desalination systems. Both uses are in line with the Horizon 2020 societal challenge of “Health, demographic change and wellbeing”. The aim of this research proposal to better understand the mode of activity/selectivity of natural ion/water channels by developing structurally simple and robust artificial foldamer-based channels. The overall research objective of this project is to attain foldamer based transmembrane supramolecular channels for ion/water transport and identify sequence-structure-transport relations. HeliTrans has following specific research objectives (SROs): SRO1: Extend channel diameter large enough to transport small molecules or ions yet long enough to span a bilayer membrane. SRO2: Undertake initial investigations of the channel transport properties through model bilayer membranes and validate membrane insertion and transport measurement protocols. SRO3: Enrich foldamer sequence information and establish sequence-structure-transport property correlations.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
- LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggCoordinatorGermany
Links
Data: CORDIS, © European Union