Biopharmaceutical HOS analysis by automated fast hydrogen deuterium exchange

Knowledge of a biopharmaceutical product’s higher order structure (HOS) and conformational dynamics, and

how these relate to it’s mode of action and/or degradation, are central to enable effective and streamlined

biopharmaceutical development through QbD-based approaches. Hydrogen deuterium exchange mass

spectrometry (HDX MS) is a technique increasingly used to characterise the HOS of peptide and protein

therapeutics. HDX MS can determine structural perturbations in a protein that elicit changes in conformational

dynamics or solvent accessibility. Commercial implementation of automated HDX MS analysis, has greatly

increased the utility of HDX MS in the biopharmaceutical industry for HOS analysis. But there are limitations

with these systems where unstructured or highly dynamic, solvent exposed protein regions are not able to be

differentiated or analysed. This team propose to develop a system that will allow routine analyse of these

proteins and peptides with HDX MS.