Investigation of Fluorinated Prolines by NMR Spectroscopy

This fully funded PhD project at the University of Southampton focuses on the investigation of fluorinated prolines (FPro) using advanced nuclear magnetic resonance (NMR) spectroscopy. Supervised by Prof. Marina Carravetta, Dr. Giuseppe Pileio, and Prof. Ilya Kuprov, the research aims to control and measure the unusual dihedral angles of proline, an amino acid with unique structural properties, by employing FPro as a proxy for natural prolines. The project addresses the presence of uncommon proline conformers in biologically active peptides, such as conotoxins and neurotransmitter mimetics found in animal venoms. By introducing various degrees of 19F substitution, the research seeks to manipulate proline's structural characteristics, leveraging fluorine's large chemical shift anisotropy (CSA) for detailed NMR analysis. Theoretical modeling, particularly using density functional theory (DFT), will be essential to account for different molecular conformations and to model FPro relaxation processes, especially those outside the scope of traditional Redfield theory. Experimental and theoretical work will proceed in tandem, with experiments conducted under varying magnetic fields, temperatures, and solvent viscosities to validate and refine theoretical models. The project will also develop and apply quantum optimal control techniques, building on fluorine-edited selective transfer approach (FESTA) methods, to address challenges such as peak overlap in complex peptide and protein systems. Further research will explore the role of proline in protein structures, particularly in sharp turns, secondary structure junctions, and disordered regions. The interactions of FPro with neighboring residues, including polyproline chains and aromatic amino acids, will be investigated to reveal important π-interactions and their effects on protein conformation and dynamics. The studentship is fully funded by The Leverhulme Trust, covering UK tuition fees (including Horizon Europe fee waiver) and providing a standard UKRI stipend for up to four years. Applicants must hold a UK 2:1 honours degree or its international equivalent. Applications should include a CV, two academic references, degree transcripts, and proof of English language proficiency if required. The University of Southampton and its School of Chemistry and Chemical Engineering are committed to equality, diversity, and inclusivity, welcoming applicants from all backgrounds and offering flexible working patterns and comprehensive support for work-life balance. The university is recognized for its sustainability initiatives and supportive environment for postgraduate researchers. For more information or to apply, visit the project page or contact the Faculty of Engineering and Physical Sciences at [email protected]. For an initial conversation about the project, contact Prof. Marina Carravetta at [email protected].