The project is at the nexus of several rapidly emerging areas: mechanically interlocked molecules, macrocyclic peptides, and supramolecular chemistry in biology. This project seeks to use cyclic peptides as the macrocycles in rotaxanes.
Student Profile
Applicants must have or be predicted to obtain a BSc or a Master’s degree with first-class honours or upper division second-class honours (2:1) in Chemistry.
Candidates should be able to demonstrate an aptitude for research, the ability to work collaboratively in a diverse research environment as well as problem-solving and independence. This position will suit a candidate with an interest in supramolecular and biological chemistry
Project Description:
We are a synthetic chemistry group working in supramolecular and biological chemistry, and nanotechnology. We work in the Francis Crick Institute in London, and at King's College London.
Our research looks at how we can apply Supramolecular Chemistry in Biological settings. Supramolecular Chemistry is the study of intermolecular, non-covalent interactions. These non-covalent interactions are critical to protein folding, DNA base pairing, and cellular signalling. Supramolecular Chemistry applies these same principles to create artificial systems capable of performing complex tasks. 1,2,3
The McTernan Group aims to apply recent breakthroughs in artificial molecular machines and metal-organic capsules in biologically relevant settings.4,5 We work with rotaxanes, catenanes and capsules to synthesise functional architectures, creating de novo catalytic enzyme analogues, artificial cellular receptors, and generating targeted drug delivery vehicles.
The proposed project is at the nexus of several rapidly emerging areas of science: mechanically interlocked molecules, macrocyclic peptides, and supramolecular chemistry in biology. This project seeks to use cyclic peptides and depsipeptides as the macrocycles in rotaxanes (where a ring encircles a linear axle). This approach will have three key benefits over the current state-of-the-art, which uses simple macrocycles . Firstly, it will vastly increase the information density and complexity of the rotaxanes that we can form, thus enabling novel functions. Secondly, introducing mechanical bonds to cyclic peptide drug molecules will act as a new approach to solve current issues of stability, toxicity and bioavailability, by providing an orthogonally tunable handle. Thirdly, this programme will act as a first step to bridge the current divide between biological molecular machines (which evolved to function in aqueous environments) and artificial molecular machines (which function almost exclusively in organic solvents), by using intrinsically water-compatible components, constructing a new language for molecular machinery.
The current generation of interlocked molecules are almost exclusively formed from highly symmetric and simple macrocycles, such as crown ethers. Whilst great progress has been made in biomedicine, technology, and molecular machinery by using information embedded in the axle, limited progress has been made with the other half of a rotaxane - the macrocyclic ring. The difficulty of selectively functionalising highly symmetric macrocycles, and often low yielding macrocyclisation reactions, have stymied progress in the area. Cyclic peptides provide a solution to both these difficulties - the synthesis of functional cyclic peptides is well established, amenable to solid-phase and high-throughput synthesis, and macrocyclisation is reliable and high yielding. As such, cyclic peptides provide an ideal platform to explore the transformative potential of highly functionalised and functional macrocycles in artificial molecular machines.
Application Procedure
To be considered for the position candidates must apply via King’s Apply online application system. Details are available at Postgraduate taught and research courses | Department of Chemistry | King’s College London (kcl.ac.uk)
Please indicate your desired supervisor and quote research group McTernan in your application and all correspondence.
Please include the project ID McTernanLever as the award scheme code under in the funding section of your application.
If you require support with the application process, please contact the Chemistry Postgraduate Research Officer Sile Maguire Conneely [Email Address Removed]
The selection process will involve a pre-selection on documents, if selected this will be followed by an invitation to an interview. If successful at the interview, an offer will be provided in due time.
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