AbstractThis thesis explores helical oligomers that can be utilised to transmit information in the form of a chiral signal. The signal is induced at one end of the molecule, and the helical conformation facilitates the transfer of this chiral input to the other end. 310 helices constructed from the quaternary amino acid Aib have been used for this purpose, as they can rapidly switch between their left and right-handed screw senses and have high helical fidelity.
To explore the limits of these oligomers as conformational communication systems, a family of molecules were synthesised that disrupted the natural N-to-C directionality found in peptides by having two opposing N-termini. It was found that communication between the two N-termini was possible, though it was much weaker when compared against standard Aib oligomers.
The ability of Aib oligomers to adapt to abnormal stereo-controllers was tested with the N-terminal hydantoins. These were found to be successful inducers that favour the opposite screw sense to their parent amino acid.
The aggregation and conformation that Aib oligomers adopt in aqueous solution was studied with the hydrophilic Aib foldamers. These showed that the 310 conformation can be stabilised even in fully aqueous solutions.
Finally, the efficacy of the AibAic foldamers as a new scaffold for conformational communication was assessed. It was found that when these foldamers were controlled from the C-terminus the signal was registered at the N-terminus. However, the rate at which the signal decayed along the foldamer was higher than previously observed for Aib oligomers.
|Date of Award||19 Mar 2019|
|Supervisor||Jonathan P Clayden (Supervisor)|