Lysine focused Covalent Fragments

Until recently, covalent binders targeting Lysine residue attracted less attention as compared to those modifying Cysteine or Serine. Being among the essential amino acids, Lysine can be found both at the surface and in active sites of many enzymes (e.g. kinases, viral polymerases and integrases, aldolases, DOPA decarboxylase, P-glycoprotein), and it can also participate in catalytic reactions. Moreover, Lys residue is often involved as a key player in many important signaling and metabolic processes. An example can be protein ubiquitination, which mainly occurs through lysine residues on substrate proteins or itself. Selective modification of Lys residue becomes more and more attractive for the investigation of many signaling processes in live cells and, potentially, can play a key role in the discovery of next-generation drugs.

Lysine focused Library is plated at 20 mM concentration in DMSO and is available for fast supply in any custom format. Compounds pooling based on delta MW can be provided as a formatting option. Please request the list of expected molecular weight shifts for MS-based screenings.

Typical Formats

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Examples of compounds in the library

To address the increased interest and need for lysine-specific covalent binders, we have synthesized several libraries bearing warheads described as selective/preferred toward Lysine. Our renewed library contains only specially synthesized compounds with Lys-specific covalent warheads. The following types of covalent binders were used for the library construction:

Salicylic aldehydes

• Lys-specific, reversible
• The o-hydroxy group stabilizes covalent adducts
• Low reactivity

Vinylsulfonamides

• Irreversible binders
• Showed some selectivity toward Lys over Cys
• Highly reactive

α-Formyl Boronic acids

• Reversible and Lys specific
• Boronic residue in α-position dramatically enhances the stability of resulting adducts

Sulfonyl Fluorides

• Irreversible binders for Lys, pH-dependent
• Reactivity depends on structure
• Compounds selected to display moderate reactivity

Distribution by covalent warhead

The library can be screened directly at Enamine in our biology laboratories, which offer a wide range of screening techniques including MS-based screening, kinetics, and intrinsic reactivity measurements. In this case, we will be happy to offer you a discount on library costs and follow-up services depending on the collaboration scope.