Cysteine-focused Covalent Fragments Library Screening

We offer Cysteine-focused Covalent Fragments Library Screening. Several classes of Cys-specific covalent electrophilic moieties able to bind cysteine residues of a protein either reversibly or irreversibly formed the basis of the Cysteine-focused Covalent Fragments Library. Covalent warheads were carefully chosen based on their reactivity and all molecules with trivial or unwanted structural features were removed from the pool of electrophilic fragments selected by structural filters. The resulting set of molecules contains 3 200 fragments.

Workflow overview:

1. Method Development using Representative Set:

  • Control compounds: supplied by Customer, or generic (N-ethylmaleimide (NEM), Iodoacetamide (IAA));
  • Array of the reaction conditions (pH, time, protein to ligand ratio, tºC);
  • Depending on the results, reaction conditions are selected for the entire library screening.

2. Screening of the whole Library on the protein target

3. Hit confirmation from DMSO stocks

4. Optional service: Promiscuous Hits Exclusion

  • Non-selective highly reactive molecules based on their intrinsic reactivity evaluation by the Ellman’s assay are classified as promiscuous hits and excluded from further studies.

5.  Deliverable: table format report, plates visualization

Cys Library Representative Set (160 compounds)

for Method Development

  • Cys Library Representative Set was carefully selected by experienced chemists for time-and cost-efficient method development;
  • The Set represents 5% of the entire Library;
  • It covers all classes of Cys-specific covalent electrophilic compounds and properly represents structural diversity of the Cysteine-focused Covalent Fragments Library.