The Chemical Proteomics unit (ChemProt) is a national unit expert on supporting drug discovery and development by proteome-wide deconvolution of targets and action mechanisms of small molecules.
ChemProt has recently developed high throughput (HT) chemical proteomics methods which outperform the previous methods for target deconvolution of at least tenfold and decrease by the same factor the time of analysis of the sample amount needed for each biological replicate. The novel methods can use a high level on multiplexing for several biological replicates, up to 16 per experiment according to the latest state of the art for quantitative proteomics. Different compounds or more than one biological system can be tested simultaneously. The LC-MS instrument park has been renewed for better supporting the new high throughput chemical proteomics.
Please feel free to contact us (firstname.lastname@example.org) and come visit us at KI Biomedicum. You will receive consultation free of charge, finding out about feasibility, details and better solutions for your project or your potential one.
ChemProt is also the national unit expert of Chemical Proteomics within the Swedish infrastructure for biological mass spectrometry (BioMS). ChemProt is responsible for the entire Chemical Proteomics technology and also provider of protein structural analysis through HDX-MS. Through BioMS and SciLifeLab we can support your project and cover relevant costs of it by national funding.
To book services of our unit please create a new application at the BioMS portal and when requested in the application form please select “Chemical Proteomics” as technology and then add “M.Gaetani” as BioMS contact.
ChemProt makes use of proteome-wide orthogonal approaches to find out how small molecules work when incubated in cell cultures and in lysates. Most approaches can be provided with no molecular modification for chemical probe engineering. ChemProt can provide full pipelines reproducing the biological treatments of the phenotype of interest or operating the treatment planned with the users. ChemProt also offers hydrogen-deuterium exchange mass spectrometry (HDX-MS) for mapping and characterizing the target binding site, and monitoring other structural changes. Our outcomes include full data analysis, high confidence identification of most reproducible and treatment-specific MoA signatures and target candidates. Follow up support for consequent experimental and publication purposes are provided; consultation is always provided on request and free of charge, also to guide further planning.
Deconvolution of compound targets, determination of mechanism of Action (MoA) and off-target landscape through orthogonal methods of mass spectrometry-based deep proteomics
Matches over two orthogonal approaches dramatically increase the chances to find the correct target. These methods are here listed:
Protein Structural Analysis using Hydrogen-deuterium exchange mass spectrometry (HDX-MS)
Using a thermal profiling (TPP or PISA) based approach in cell lysate and recombinant enzymes and their co-factors (Saei AA et al, submitted; BioRxiv: DOI: 1101/423418 )
(e.g. PTMs, deep quantitative proteomics, etc.)
ChemProt laboratories are at located at the Department of Medical Biochemistry and Biophysics (MBB) of Karolinska Institutet, Biomedicum. ChemProt represents an innovative unit model offering complete pipelines and including different laboratories for cell culture, sample preparation, LC-MS and bioinformatic analysis.
Cell culture lab Instruments: Two laminar flow cabinets, Two CO2 incubators, Two Microscopes, Eppendorf centrifuge, BioRad cell counter, etc.
Centrifuges: Beckmann XPN-80 ultracentrifuge, Speedvac centrifuges , Eppendorf centrifuges for large and small tubes
HDX-MS Robot: CTC PAL Liquid Handling System connected to a Peltier-cooled box
Data Analysis Harware and Software: Four PC stations, Proteome Discoverer 2.4, BioPharma Finder, Peaks, MaxQuant, Mascot, SIMCA, GraphPad PRISM, Excel, R, etc.
From October 1, 2020 new guidelines are applied, in line with the guidelines introduced by KI on 1/1/2018.
After an initial discussion of the project and before sample submission, the user is kindly requested to provide a brief description of the project and for that provided with a project description template and necessary help for its completion. The final project description will undergo internal unit approval and necessary suggestions to optimize the project design and maximize data quality and scientific impact of the unit application in the project.
The user could choose different levels of services, summarized below:
The unit can also be engaged with Collaborative research, meaning that the unit is part of a grant application together with the collaborator(s) and all costs are already defined and given upfront of the analysis after grant approval.
Chemical Proteomics, MBB
171 77 Stockholm
Chemical Proteomics, MBB
171 65 Solna