An effective strategy for enhancing the potency and selectivity of initial active molecules is via covalent bond formation with a nucleophilic residue that is specific to a target of interest and ideally showing no off-target interactions [1-3]. Such covalent-binding chemical probes have increasingly been used in proteome-wide target identification and imaging as well as for finding inhibitors with high specificity among related enzymes and enzyme isoforms .
Life Chemicals has designed its Serine Focused Covalent Library on the basis of a combination of specific structural fragments (functional groups or covalent “warheads”) that were reported to form covalent bonds with a serine residue in binding sites of proteins [5-7] and drug-like filters.
Over 2,700 small-molecule screening compounds with the following structure fragments were included in the Library:
|Figure 1. Compound distribution by different chemical classes within the Library|
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