Chemical Proteomics

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.

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) 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:

- 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;
- Target characterization by top-down proteomics;
- Interaction interface elucidation by HDX MS analysis.

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.

References:

1. (a) Koshland, DE. Application of a Theory of Enzyme Specificity to Protein Synthesis. PNAS, 1958, 44, 98, 104. b) Linderström-Lang, K.; Schellman, J. A. Protein structure and enzyme activity. The Enzymes. 1959, 1: 443.

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.