| Summary: | This thesis details work carried out with the aim of demonstrating electronic control of protein interactions. A pair of coiled coil peptides including an acidic peptide and an alkaline peptide were designed and synthesised. Characterisation studies were carried out in solution using CD and FRET, which showed that heterodimers were preferentially formed at neutral and weakly alkaline pH and that homodimers of the alkaline peptide were preferentially formed at strongly alkaline pH. This demonstrated that the peptides had pH dependent binding behaviour, as intended. Characterisation was then performed using FRET, SPR, and CD with the alkaline peptide immobilised on surfaces. It was shown that the pH dependent binding behaviour was retained, with the acidic peptides dissociating from the alkaline peptide monolayer only above a certain alkaline binding pH. This binding pH was typically lower than the pH at which homodimer preferentially formed in solution and could be changed by varying the concentration and pH at which the monolayers were formed. This led to the conclusion that the binding pH depended on the density of the monolayer. Experiments were performed to demonstrate that the pH of a solution in the vicinity of an electrode could be changed electrochemically and measured using optical techniques. It was shown that the pH changes immediately at the electrode surface were significantly larger than those observed further into the solution. Monolayers of heterodimers were then immobilised on electrodes via the alkaline peptide and it was demonstrated that the acidic peptide could be removed from the monolayer by application of a current to the electrode. Control experiments demonstrated that the removal of the acidic peptide was caused by the pH change at the electrode surface that was induced by the current application. Electronic control of protein interactions was therefore demonstrated.
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