Mass Spectrometry-based approaches to facilitate better construct design for stable protein variants.

Mass spectrometry is a central analytical technique for protein research. It is the most comprehensive approach for quantitative and qualitative analysis of proteins, their interactions and modifications. Within AstraZeneca Discovery Biology Protein Science team we utilise various aspects of mass spectrometry generated data to facilitate protein generation and characterisation for downstream early drug discovery applications. We employ techniques based on Hydrogen Deuterium eXchange MS, native MS, peptide mapping and intact mass measurements to help us generate stable protein truncation variants amenable for large scale expression and purification. We are also looking into introducing targeted mass spectrometry approaches to generate quantitative data indicative of expression levels for our recombinant proteins of interest.