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Quantification of peptide secondary structure: The use of solid and solution state NMR to develop ATR FTIR spectroscopic methods.

Supervisor: Józef Lewandowski, Stephanie Brookes (AstraZeneca)

Transmission FTIR spectroscopy is a well-established technique for quantification of protein/peptide secondary structure in the solution state. However, within AstraZeneca it is often necessary to acquire data using the attenuated total reflectance (ATR) technique. This is required both when analysing solid materials and when analysing viscous solutions or samples that may precipitate or fibrillate blocking a narrow path length transmission cell. Recent work has demonstrated that ATR spectra cannot be modelled successfully with existing transmission models due to the significant shift of intense infrared absorption bands that can occur with the ATR technique. Both solid and solution state NMR offer the potential for accurate quantification of peptide secondary structure. However quantification is not trivial often requiring synthesis of labelled materials as well as complex data modelling. The aim of this PhD is to investigate whether NMR can be used to accurately quantify the secondary structure of a range of proteins and peptides in both solution and the solid state in order to build models for FTIR ATR data. The student will gain experience of a wide variety of analytical techniques in order to characterise the samples including X-ray crystallography and circular dichroism as well as NMR and FTIR methods. In addition the student will develop skills in sample preparation and data analysis and will also collaborate with external companies to investigate whether it is possible to correct data accurately for the ATR effect.

This position has now been filled.