The evolution of drug resistant pathogens creates the need for the introduction of new antimicrobial drugs. Peptaibols, a class of naturally occurring peptides, contain large amounts of alpha aminoisobutyric acid (Aib). They are known to exhibit their antimicrobial activity by perturbing the membranes of pathogens. However, a comprehensive model of action for these peptides has not yet been identified. Aib residues support the formation of 310-helix conformation and it is thought that this secondary structure is important for their antimicrobial activity. It is possible to design small synthetic peptides, known as foldamers, endowed with specific properties; in particular, Aib-rich foldamers are used as a model for the understanding of the folding and membrane interaction of the naturally occurring species. The aim of this thesis is to investigate the conformational preference of monodisperse Aib-oligomers as well as understanding their interaction with bilayer membranes.A large set of spectroscopic techniques have been used to establish the conformation of Aib-rich foldamers both in solution and when bound to membranes. In particular: Raman, Raman Optical Activity (ROA), Infrared (IR), Vibrational Circular Dichroism (VCD), Linear Dichroism (LD) and Neutron Scattering (NR) were employed to provide new structural insights.These vibrational analysis (VA) and vibrational optical analysis (VOA) investigations in solution were focused on the identification of spectral features for 310-helix conformation, particularly with Raman and Raman Optical Activity spectroscopies. Spectroscopic markers for this conformation in the amide I region were successfully identified. Moreover, it is known that chiral Aib-rich peptides can show a right or left handed screw-preference based on the primary sequence. VOA studies successfully distinguished between peptides with opposite helicity.VCD, ROA, LD and NR of Aib-foldamers bound to membranes were shown to be useful for identification of conformational preferences of the peptides within the membrane as well as for determining their orientation in the bilayer, and ultimately the effect of the peptides on the membrane structure.
|Date of Award||1 Aug 2017|
- The University of Manchester
|Supervisor||Simon Webb (Supervisor) & Jonathan Clayden (Supervisor)|
- Raman, Raman Optical Activity, Spectroscopy, Peptides, Peptibols, Linear dichoroism, Neutron Scattering
- membranes interactions