From LiP-MS to TrueTarget™ – A Novel Platform for Drug Target ID and Proteome Exploration in 3D

A key step in the drug development pipeline is having a deep understanding of a compound’s target protein space including target identification, protein binding affinities and binding site affirmation. Traditionally, this pathway from small molecule target deconvolution to binding site characterization has been highly time and labour intensive. Proteomics-based strategies have gained popularity in recent years as robust and highly sensitive techniques that can provide vital compound target information. Limited proteolysis (LiP-MS) is a peptide-centric strategy that exploits 3D structural alterations and steric hindrance induced by drug binding to determine protein binding, estimate affinity (EC50) and predict binding sites from across the proteome.

Traditional LiP-MS is an unbiased, label-free mass spectrometry-based technique that uses machine learning derived parameters to not only characterize a compound’s target protein space but also to rank proteins based upon these known parameters. To date, LiP-MS has been used extensively to characterize small molecules across species including recently published data using a novel CDK9 inhibitor developed by AstraZeneca. A LiP-MS-specific attribute that can be exploited to add significant value during drug development is its peptide centric approach, as LiP peptides often contain critical information beyond simply their protein source. This peptide-level resolution can be used to characterize drug-protein interactions through a novel high-throughput technique known as high-resolution LiP (HR-LiP).

Short Bio Nigel Beaton, PhD:

Nigel obtained his BSc (Hons) in physiology from the University of Western Ontario in London, Canada. He then received his MSc in Bioengineering from University of Strathclyde in Glasgow, Scotland before moving on to a PhD in Translational Biomedicine at ETH Zurich in Switzerland where he focused on obesity and diabetes. He continued his training as a post-doc studying the role lncRNAs play in acute-on-chronic liver failure (ACLF) at University College London in England. He joined Biognosys in 2017, working as a senior scientist developing their limited proteolysis platform for target deconvolution and structural proteomics. He currently works as a scientific director at Biognosys.

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