The functional units of life, proteins, play a fundamental role in every biological process from development and homeostasis to disease progression and memory formation. The keratin that comprises hair and the enzymes that enable digestion represent just a fraction of the vast protein repertoire found within humans, each with specific functions that are estimated to number over a million. While the human genome codes for only around 19,000 proteins, post-translational modifications expand this range by orders of magnitude. The proteome, the collective term for the proteins comprising a cell, tissue, or organism, governs the health of an organism and is a source of intense scientific attention. Proteomics, the systematic study of the proteome is a rapidly expanding, powerful discipline that is set to transform modern medicine and drug discovery.
Pharmaceutical R&D entails the development of therapeutic agents that interact with pathological disease mechanisms. This process is supported by proteomics, which can discover novel targets, identify disease mechanisms, and reveal the function of lead compounds through mechanism of action studies. From this paradigm emerged pharmaceutical proteomics, a field that utilizes proteomic technologies for drug discovery and development.
Proteomics allows us to get closer to the true phenotype and gain better understandings of diseases and develop better drugs.
A proteomic profile provides information about all of the detectable proteins that are produced in a cell or tissue. Accordingly, it can provide invaluable insight into the contents of a clinical specimen and determine states of disease or understand how an individual responds to a given drug. Specifically, by observing alterations in protein levels, it is possible to identify biomarkers of disease that can inform disease progression and treatment options. This has considerable applications in the field of drug discovery, as it can allow the early detection of toxic compounds in the pipeline, thereby expediting the withdrawal of unsuitable drugs and fast-tracking more promising alternatives.
Obtaining a proteomic profile can be achieved in a number of ways. At Biognosys, its proprietary Hyper Reaction Monitoring (HRM) workflow offers an unmatched proteome coverage that allows the precise quantification of up to 10’000 proteins per sample. This method employs liquid chromatography to separate peptides and high-resolution mass spectrometry to record peptide ion signatures.
Once a biological or therapeutic protein of interest has been identified, understanding its function is an important next step in drug development. This can be achieved through functional proteomics. The biological function of proteins, protein groups, and protein classes can be determined at this stage, as well as the cellular mechanism at the molecular level. Altogether, this can aid in determining the target drug-ability and discovery of lead compounds. This has substantial application in anti-cancer drug discovery, where functional proteomics can facilitate the detection of in vitro and in vivo cancer cell-specific toxicity.
A great example of such a workflow would be limited proteolysis technology coupled with next-generation quantitative mass spectrometry (LiP-MS) which allows for unbiased structural protein profiling across the entire proteome.
Profiling and functional proteomics are invaluable for resolving protein-level drug mechanisms and exposing toxic compounds. At Biognosys, we are committed to accelerating and de-risking drug research and development by adding precision to drug discovery workflows.
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