The appearance of cell membranes during prebiotic evolution was essential for the emergence of cellular life, but made the transfer of molecules and information across these barriers necessary. One way of communicating information between cells is the transport of ions through the phospholipid bilayer that comprises the cell membrane. Nature uses different mechanisms for the process of ion/molecule transport. The most common transport system found in nature are ion channels. Since natural occurring ion channels are very complex and therefore difficult to analyse, we synthesised artificial ion channels and tested them for their behaviour in phospholipid bilayers and their biological activity. Taking nature as a role model, for the presented PhD project, molecular motifs from the naturally-occurring peptaibol, alamethicin have been adopted. This pore-forming antibiotic has a high proportion of Î±-aminoisobutyric acid (Aib) and produces ion channels in cell membranes that give its antibiotic activity. Therefore, several Aib-foldamers have been synthesised and analysed for ion channel as well as antibiotic activity. Moreover, the compounds were tested for their hemolytic behaviour, since alamethicin itself is toxic to humans due to its hemolytic effect. Furthermore, Aib foldamers with a chelating head group were designed to achieve a simple approach to producing a variety of different metal-complexing compounds in a simple way. Here, Co(II), Ni(II), Cu(II), Cu(I) and Zn(II) were chosen as metal ions, with chloride as the counter ion. These different derivatives showed significant variation in their activity. Besides, the Cu(II) species were used to develop a switchable ion channel, which can be triggered by a Cu(II)/EDTA-system.
|Date of Award||1 Aug 2019|
- The University of Manchester
|Supervisor||Simon Webb (Supervisor) & Lu Shin Wong (Supervisor)|
- Aib, Foldamers, Antiiotics, Ion Channels