HDXperts AB offers Chemical Proteomics Services
Chemical proteomics involves powerful approaches based on mass spectrometry and employed for identifying proteome-wide compound-target interactions and compound effects.
Chemical proteomics includes:
Compound-centric approaches using either modified, tagged compounds as baits to identify target proteins that bind to them in a proteome-wide background, or more modern approaches employing unmodified molecules;
Activity based approaches, where molecules of interest induce changes in the activity status of various enzyme families;
Thermal-shift based assays, exploiting the fact that the binding of low molecular weight ligands can increase the thermal stability of a protein, as described by Koshland (1958) (Reference 1a) and Linderstrom-Lang and Schellman (1959) (Reference 1b).
Recently, quantitative expression proteomics has emerged as a powerful tool for unbiased drug target deconvolution, such as the Functional Identification of Target by Expression Proteomics (FITExP)2 assay, where compound-induced changes in the protein abundances are measured. To complement the comprehensive target analysis, our unique hydrogen-deuterium exchange mass spectrometry (Reference 3) platform determines the site of drug binding to protein and kinetics of the site-specific interactions.
At the moment, HDXperts offer the following services:
- Thermal shift analysis based on ligand-protein interaction;
- FITExP for identification of the drug target and compound’s mechanism of action.
- Identification of the cellular death pathway by full-proteome mapping on an database containing cellular responses to main classes of anti-cancer compounds and non-molecular treatments, such as hyper-thermia and starvation;
- Target characterization by top-down proteomics;
- Interaction interface elucidation by HDX MS analysis.
In summary, we have a strong background in Chemical proteomics and have developed or implemented sophisticated approaches with a potential to accelerate drug discovery.
The expected user base: the country-wide as well as international community of industrial researchers active in the area of drug discovery and drug development.
1. (a) Koshland, DE. Application of a Theory of Enzyme Specificity to Protein Synthesis. PNAS, 1958, 44, 98â€“104. b) LinderstrÃ¸m-Lang, K.; Schellman, J. A. Protein structure and enzyme activity. The Enzymes. 1959, 1: 443â€“510. c) Savitski M. M. et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science. 2014, 346: 6205. d) Huber K. V. et al. Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling. Nat. Methods. 2015, 12:1055-7.
2. (a) Chernobrovkin, A. L.; Marin Vicente, C.; Visa, N.; Zubarev, R. A. Functional Identification of Target by Expression Proteomics (FITExP) reveals protein targets and highlights mechanisms of action of small molecule drugs, Scientific Reports, 2015, 5, article 11176. (b) Lyutvinskiy, Y.; Yang, H.; Rutishauser, D.; Zubarev, R. A. In silico instrumental response correction improves precision of label-free proteomics and accuracy of proteomics-based predictive models, Mol. Cell Proteomics, 2013, 12, 2324-2331.
3. Cherry, A. L.; Finta, C.; Karlstrom, M.; Jin, Q.; Schwend, T.; Astorga-Wells, J.; Zubarev, R. A.; Del Campo, M.; Criswell, A. R.; de Sanctis, D.; Jovine, L.; Toftgard, R.Â Structural Basis of SUFU-GLI Interaction in Human Hedgehog Signaling Regulation, Acta Crystallographica D, 2013, 69, 2563-2579. Other references to our collaborators can be found here.