Periodic Reporting for period 1 - HeliTrans (Helical foldamers with tunable channels for transmembrane water and ion transport)
Berichtszeitraum: 2022-06-01 bis 2024-05-31
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.
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.
Our idea is to prepare the very first structurally defined, tunable, membrane spanning unimolecular channels. HeliTrans delivers key design principles, leading on to the synthesis of longer foldamers for ion/water transport. To obtain the target oligomers, several monomers were synthesized. Segment amide coupling was used to obtain a prototypical first-generation oligomer.
By end of this project, HeliTrans will deliver very first foldamer based membrane spanning unimolecular ion/water channels. HeliTrans is primed to produce potentially useful and high-impact results in the area of foldamers chemistry and artificial transmembrane channels. The results coming out of this project will feature ready applicability in future research on these two fields and beyond. Though candidates for channel replacement therapies seem remote, the application of selective water transport for desalination is much more straight-forward. It is expected that this project may significantly improve design capabilities towards this goal.