Hydrophobic cholate scaffolds anchor these synthetic channels-formers in the membranes of cell-mimetic phospholipid vesicles.
Controlled communication between cells is vital for a host of biological processes, and two key methods used by cells to communicate are the transport of ions across the membrane or conformational/positional changes in membrane proteins. The first method requires fine control of the influx and efflux of ions and small molecules into and out of cells. An example is the propagation of neural signals through synaptic gap junctions, which relies on the controlled movement of ions such as sodium or potassium through the cell membrane. Our interests lie in developing synthetic ion channels which can be opened and closed by external stimuli. We have recently published work describing novel pyridyl-functionalised cholic acid-based ion channels that could be opened by palladium(II), which allowed transport of ions into phospholipid vesicles. We are now looking to develop new ion channels that contain different gating motifs and/or link vesicles together, which will copy gap junctions and ultimately provide functional tissue mimics.
Top: Generalised structure of Aib oligomers that are able to insert into phospholipid bilayers. Bottom: Interconversion of helical Aib peptide secondary structures by covalent and non-covalent control.
The second method requires an external ligand to bind to and induce a conformation change in a membrane-spanning protein, which is transmitted to the interior of the cell and initiates a cascade of enzymatic transformations. In conjunction with Prof. Jonathan Clayden, we aim to design and synthesise a series of conformationally-responsive helical peptides, which will mimic the signal transduction mechanisms of G-protein coupled receptors upon receipt of an external chemical signal.
Pd(II)-mediated assembly of porphyrin channels in bilayer membranes.
Langmuir 2011, 27, 1448-1456.
Palladium(II)-mediated assembly of biotinylated ion channels.
Chem. Eur. J. 2011, 17, 3465-3473.
Palladium(II)-gated ion channels.
Chem. Commun. 2008, 4007-4009.