Chemical Proteomics

  • Nordic Preclinical Sciences AB can help you to find out how your small molecules work when incubated in cell cultures and in lysates. 
  • Most approaches can be provided with no molecular modification for chemical probe engineering. 
  • We can provide you the full pipelines reproducing the biological treatments of the phenotype of interest. 
  • We can also provide hydrogen-deuterium exchange mass spectrometry (HDX-MS) for mapping and characterizing the target binding site, and monitoring other structural changes. 
  • We will provide you full data analysis, high confidence identification of most reproducible and treatment-specific MoA signatures and target candidates. 

TECHNOLOGIES AND SERVICES

Deconvolution of compound targets, determination of mechanism of Action (MoA) and off-target landscape through orthogonal methods of mass spectrometry-based deep proteomics:

  • Protein solubility/stability alteration signatures in treated cell cultures and lysates.
  • Treatment-specific expression/degradation proteome signatures.
  • Changes in proteome redox balance in treated cell cultures.

Drug Target Finding

Matches over two orthogonal approaches dramatically increase the chances to find the correct target. These methods are here listed:

  • FITExP, based on compound-specific proteome responses and with no need of chemical engineering of compounds (now up to 16-plex) (Chernobrovkin A et al., Sci Rep, 2015, DOI:1038/srep11176 ).
  • ProTargetMiner, high throughput method to study anticancer compounds based on FITExP-derived database of proteome signatures using a library of anticancer molecules (Saei AA et al., Nat Commun, 2019; DOI:1038/s41467-019-13582-8).
  • Identification of interactions and protein complexes after affinity-based approaches using chemical engineered probes (now up to 16-plex).
  • RedOx Proteomics, for specific proteome changes in the reduction-oxidation balance.

Protein Structural Analysis using Hydrogen-deuterium exchange mass spectrometry (HDX-MS)

  • Binding site mapping and characterization for: protein-small molecule interactions; protein-peptide interactions; protein-protein interactions, including epitope mapping.
  • Conformational changes monitoring to study effects of mutations, to analyze misfolding and for biosimilar characterization.