Cambridge Healthtech Institute’s Kent Simmons recently spoke with Dr. Zhe Zhang, a Senior Scientist in the Integrated Biologics Profiling group at Novartis, about his upcoming presentation “Top-Down Mass Spectrometry Strategy for Novel Drug Characterization”, to be delivered in the Characterization of Biotherapeutics meeting at the 2018 PEGS event. PEGS is scheduled for April 30 - May 4, 2018 in Boston, with the characterization program set for April 30-May 1.
What are some highlights from your upcoming talk?
In my talk, I will share the Developability Assessment concept we use at Novartis and discuss the utilization of top-down mass spectrometry (MS) in two of our group’s recent projects.
What is top-down mass spectrometry? What is the difference between top-down mass spectrometry and other mass spectrometry techniques?
Traditionally, bottom-up MS has been a well-established technology used to obtain residue information. In bottom-up strategy, a protein needs to be digested into peptides, followed by peptide separation prior to MS analysis. These procedures require more effort and also could introduce method artifacts compared to top-down MS. The emergence of top-down MS provides an alternative tool and unique benefits.
Top-down MS features analyzing proteins by tandem MS (i.e. MS/MS). The idea is to use ionization technique to introduce intact protein ions in mass spectrometer, followed by dissociating protein ions and then analyzing protein ion fragments. Therefore, residue-related information can be revealed by analyzing protein fragments. It is an emerging technology which requires high-performance instrumentation. Recent advances in mass spectrometer instrumentation (e.g. ion isolation, fragmentation, and resolution) facilitate the success of top-down MS.
What kinds of problems have you solved with top-down mass spectrometry?
Starting from early 2000s, top-down MS has been developed for various applications. It can investigate sample identities, study post-translational modifications, and perform relative quantitation. In one of the projects that we worked on, one candidate was found to have severe clipping problem with unknown sites, top-down MS helped us identify the exact clipping sites. In another project, top-down MS showed its ability to identify oxidation location on a drug candidate.
What are you most looking forward to at the PEGS Summit?
I am looking forward to learning the trends and perspectives of early drug development during this international leading conference. Topics such as how to optimize early drug development, what to learn from past projects, and how new technology can change the drug discovery and development routine would be interesting to me.
Speaker Biography:
Zhe Zhang, PhD, Senior Scientist, Integrated Biologics Profiling, Novartis
Zhe Zhang works in Novartis focusing on biologics developability assessment since 2016. In Integrated Biologics Profiling (IBP) group, Zhe provides profiling analysis for protein drug candidates by mass spectrometry. Before joining Novartis, Zhe received his Ph.D. in Chemistry from University of Massachusetts Amherst focusing on mass spectrometry application for protein aggregation characterization. Zhe also earned his B.S. in University of Science and Technology of China.