Description: Lysine is the second most common target residue used in the design of TCIs and related covalent ligands. Its appeal lies in its abundance in human proteins, which is approximately three times higher than that of cysteine (5.8% vs. 1.9%). This significantly increases the number of proteins suitable for covalent targeting, especially given that many human proteins lack ligandable cysteine residues. Moreover, it has been suggested that functional lysines have a lower probability of being replaced by mutation, as they often play a crucial role in catalysis by acting as bases or nucleophiles. Additionally, lysines are essential for maintaining the structural integrity of proteins and for regulating post-translational modifications (PTMs). Consequently, targeting lysine has garnered significant interest in recent years.
Lysine is the second most common target residue used in the design of TCIs and related covalent ligands. Its appeal lies in its abundance in human proteins, which is approximately three times higher than that of cysteine (5.8% vs. 1.9%). This significantly increases the number of proteins suitable for covalent targeting, especially given that many human proteins lack ligandable cysteine residues. Moreover, it has been suggested that functional lysines have a lower probability of being replaced by mutation, as they often play a crucial role in catalysis by acting as bases or nucleophiles. Additionally, lysines are essential for maintaining the structural integrity of proteins and for regulating post-translational modifications (PTMs). Consequently, targeting lysine has garnered significant interest in recent years.
Through careful selection, we constructed a structural filter containing over 110 electrophilic groups. By analyzing the electrophilic fragments selected by the structural filter, we removed any molecules with trivial or undesirable structural features. Ultimately, we obtained 445 fragment molecules which can target lysine residue and can be used for fragment-based covalent drug discovery.
Advantages:
- A unique collection of 445 fragments that show covalent binding with lysine.
- Careful selection of warheads: only those with experimentally validated reactivity are chosen, avoiding over-reactive warheads and any alternative reactive functionalities.
- A useful tool for the fragment-based approach to drug discovery (FBDD).
- All compounds are available off the shelf.
- LCMS or NMR validated to ensure high purity and quality.
Formulation: This fragment library containing 445 fragments with warheads targeting lysine residue.
Layout: 96-well storage tube or 96-well plate: 1st and 12th column are left empty. 384-well plate: the first two columns and the last two columns are left empty. Compounds with different concentrations or dissolved in different solvents will be put on separate plates. This way of layout may increase the number of plates because there could be three solvents and three concentrations. If you have other requirements, please let us know.
Container: 96- or 384-well Plate with Peelable Foil Seal; 96-well Format Sample Storage Tube With Screw Cap and Optional 2D Barcode.
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