HDX-MS in Pharmaceutical Analysis: Defining the Epitopes of Drug-Bound Proteins

摘要

HDX-MS was used to map out distinct areas of Bcl-xL that interact with two small drug-like molecules and one peptide. A conformational change was also observed, in agreement with previous X-ray structures. ETD fragmentation data was obtained on several peptides; by quantifying HDX for each fragment, individual amino acid residues involved in the interaction could be identified. Thus, HDX-(ETD)-MS is clearly a useful and powerful tool in the analysis of protein-drug complexes. Currently, ETD is limited to a targeted approach due to poor sequence coverage and data processing issues.