Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy
This interactive session will bring together the MS community to discuss some of the most popular and exciting peer-reviewed publications in a friendly and open forum. Ahead of each meeting, we will send out a link to the discussion article, then during the session an expert will summarise the main findings and answer your questions.
Be prepared make sure you read Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy
We're going to be joined by Dr Rebecca Beveridge from the University of Strathclyde, a senior lecturer with a host of experience with development of native ion mobility mass spectrometry methods to study proteins and protein complexes
This paper describes how Waters' SYNAPT MS can be utilized demonstrate the strength of native mass spectrometry to delineate the complex binding mechanisms of protein degraders, involving the formation of three-component protein−ligand complexes.
Reasons to Attend:
- Debate some of the most topical papers from all-time favourites to some of the latest releases
- Focus on understanding the benefit of SYNAPT MS and how to get the most out of the system for native mass spectrometry and biomolecule analysis
- Gain a greater understanding of applications and technologies by asking questions of the authors and/or expert panel
- No pre-recorded content, authors will be LIVE and on camera to answer questions
Abstract Protein degraders, also known as proteolysis targeting chimeras (PROTACs), are bifunctional small molecules that promote cellular degradation of a protein of interest (POI). PROTACs act as molecular mediators, bringing an E3 ligase and a POI into proximity, thus promoting ubiquitination and degradation of the targeted POI. Despite their great promise as next-generation pharmaceutical drugs, the development of new PROTACs is challenged by the complexity of the system, which involves binary and ternary interactions between components. Here, we demonstrate the strength of native mass spectrometry (nMS), a label-free technique, to provide novel insight into PROTAC-mediated protein interactions. We show that nMS can monitor the formation of ternary E3-PROTAC-POI complexes and detect various intermediate species in a single experiment. A unique benefit of the method is its ability to reveal preferentially formed E3-PROTAC-POI combinations in competition experiments with multiple substrate proteins, thereby positioning it as an ideal high-throughput screening strategy during the development of new PROTACs
Presenter: Dr Rebecca Beveridge (Senior Lecturer, University of Strathclyde)Rebecca is a Senior Lecturer and UKRI Future Leaders Fellow who joined the University of Strathclyde in June 2020 as a Chancellor's Fellow. She obtained a BSc in biochemistry and chemistry from the University of Leeds in 2011 and completed her PhD at the University of Manchester in 2015. Rebecca spent 4 years at the Institute for Molecular Pathology in Vienna, Austria as a postdoctoral researcher/ Lise Meitner Postdoctoral Fellow. Throughout her career, she has collected experience in a plethora of mass spectrometry methods to study protein structure such as native mass spectrometry, ion mobility, hydrogen-deuterium exchange, and crosslinking.Rebecca’s current research is centered around the development of native ion mobility mass spectrometry methods to study proteins and protein complexes, particularly those that are challenging to study with conventional biochemistry methods.
Such systems include intrinsically disordered proteins that exist in a wide range of different shapes, and protein complexes formed by protein-degrading molecules such as PROTACs, the complex binding modes of which are challenging to delineate.
