The project:
Exploiting Dynamic Stereochemistry - Mimicking Biological Function in Synthetic Molecular Systems
Biology manipulates information using conformational change to modulate interactions between proteins and other biomolecules. Synthetic systems are so far much less sophisticated, but intermolecular communication of information over long distances using conformational change has been established in peptidomimetic structures known as dynamic foldamers. Recent results have thrown light on the ability of peptide-like foldamers to form supramolecular structures, suggesting that dynamic control of conformation and therefore function may be possible in supramolecular assemblies.
The project will involve the design and synthesis of functional dynamic foldamers based on non-proteinogenic amino acids. Features designed to promote binding and assembly will be incorporated by employing ‘bespoke’ amino acid residues that will be synthesised by new methods based on our own reported routes. Selective labelling will also allow us to use NMR techniques to explore dynamic processes. Further switchable functionality (photoswitches, acid/base sensitive sites, ligand or metal binding sites) will be introduced with the aim of using chemical signals to induce gross structural change, and hence modulation of binding or catalytic activity, or of physical properties (eg micelle formation or membrane permeability) using chemical signals.
The project will entail synthetic chemistry applied to extended target molecules, NMR studies of their conformation, and other techniques (eg CD) for exploring higher order structure and binding. It will suit an ambitious graduate student interested in applying concepts in synthesis and stereochemistry in an interdisciplinary setting, extending the usual range of synthetic targets to molecules of designed structure with novel function.
References to previous work in the field:
Chem 2021, 7, 2460-2472; J. Am Chem. Soc. 2018, 140, 3528-3531;
Nature Chemistry 2017, 9, 420-425; Science 2016, 352, 575-580
Applicants should have a strong Masters degree in Chemistry.
To apply, follow this link: https://www.bristol.ac.uk/study/postgraduate/apply/
Applications will be considered as soon as they are submitted, so early applications are advised, but there will be a hard deadline of 31 Jan 2022.
Contact [Email Address Removed] for any further enquiries
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