OCT 25, 2018 9:00 AM PDT

Advances in Hydrogen-Deuterium Exchange Mass Spectrometry That Can Improve Studies of Biosimilars and Membrane Protein Drug Targets

Speaker
  • Research Chemist, IBBR Fellow, Institute for Bioscience and Biotechnology Research, BioProcess Measurements Group, Biomolecular Measurement Division, National Institute of Standards and Tech
    Biography
      Dr. Jeffrey W. Hudgens conducts research on hydrogen-deuterium exchange mass spectrometry (HDX-MS) with the aim of improving its application in drug research, quality control, and biosimilarity determinations. He is a Fellow of the Institute for Bioscience and Biotechnology Research and an employee of National Institute of Standards and Technology. He is a Fellow of the American Physical Society.

    Abstract

    Hydrogen-deuterium exchange mass spectrometry (HDX-MS) has developed into a powerful tool for investigating biopharmaceuticals, protein interactions, and membrane protein dynamics. Since 2010 HDX-MS data has helped substantiate and protect >110 US patents. Increasingly, biopharma companies provide HDX-MS data to support their biologics license applications (BLAs). However, for HDX-MS to emerge as a tool for quality control and similarity evaluations of biotherapeutics, an understanding of HDX-MS reproducibility is needed. NIST has determined the precision of bottom-up HDX-MS (Figure 1) by the analysis of 78,900 peptide measurements from 15 laboratories. We have also developed improvements to HDX-MS methodology, including automated measurements of membrane protein drug targets and chromatography instrumentation, operating at -30 oC, that improves HDX-MS measurements by arresting back-exchange.

    Learning Objectives: 

    1. An interlaboratory comparison involving 15 laboratory cohort has established reproducibility of HDX-MS, facilitating its use in commerce.
    2. NIST has developed a method that allows automated HDX-MS studies of membrane proteins, which comprise 60% of all drug targets.
    3. Chromatography  at -30 oC reduces H for D back-exchange to 5 %, which improves the  D-uptake measurement by 3x to 10x. 


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