- Other biological sciences
- Other natural sciences
Disordered proline-rich proteins play an important role in biology, as they are often involved in protein-protein interactions that mediate cell signalling or gene regulation. Using NMR spectroscopy to investigate them is obstructed by the lack of an amide proton in Pro residues and the low resolution between resonances of different residues. This project proposes introducing various fluorinated prolines (FPro) in proline-rich or oligoproline sequences, where they function as resolved NMR probes or as predictable structure modulators. The aim is the development of a strategy that recovers NMR as a tool to study the conformational and dynamical properties of disordered proline-rich peptides based on scalar and residual dipolar couplings. We already achieved synthesis of several FPro building blocks, developed new NMR techniques for extracting couplings from crowded spectra, and demonstrated the potential of FPros for structural biology studies. However, a detailed and concerted spectroscopic and ab initio analysis of the conformation and dynamics of the many FPro building blocks is essential to develop an NMR toolbox for oligoprolines. This PhD project focuses on fully characterising each FPro, developing the means to accurately interpret the experimental NMR data obtained from model peptides. The methodology will be directly applied to investigate the conformation and dynamics of fluorinated oligoprolines, and the effects of Ser phosphorylation within a proline-rich peptide.