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Lysine focused Covalent Fragments

A unique set of 640 Lys specific binders

1 550 compounds

Until recently, covalent inhibitors targeting lysine side chain attracted less attention as compared to those modifying cysteine or serine residues. Meanwhile, lysine residue is found both at the surface and in active sites of many enzymes (e. g.some kinases, viral polymerases and integrases, aldolases, DOPA decarboxylase, P-glycoprotein), as well as in the “hot spots” of protein-protein interactions. To address the increased interest to the lysine covalent modifiers, we have designed our Lysine focused covalent fragment library.

The following “warheads” were used for substructure searches of the compounds to be included into the library:

Common electrophiles

  • Vinyl sulfones and sulfonamides
  • Acrylamides
  • β-(Dimethylamino)crotylamides and -enones
  • Propargylamides
  • Sulfonyl fluorides
  • Arenesulfonates
  • Haloacetamides
  • Cyanamides
  • Azine-derived nitriles

Specific electrophiles

  • Succinimides
  • Thioesters
  • Salicylic aldehydes
  • o-Carbonylboronic derivatives
  • Saccharine (benzo[d]isothiazole 1,1-dioxide) derivatives

Further selection process included filtering by molecular parameters according to the extended Ro3 indicated for General covalent fragment library, removal of trivial chemotypes and visual inspection to avoid over reactive entities.

Examples of the molecules

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