Chromodomain is originally described as a structural motif found in Drosophila proteins with gene-silencing functions. The human proteome contains 55 chromodomain-containing proteins, including Polycomb and HP1 (Heterochromatin Protein 1) homologs. A key function of many chromodomains is the recognition and binding (reading) of methylated lysine residues by targeting different protein complexes to particular sites on chromatin, which is a key event in the reading process of epigenetic marks. A complete chromodomain structure is essential for these functions. Previous research has established the feasibility of targeting epigenetic reader protein bromodomains, which inspires a research strategy expected to discover inhibitors of chromodomains found in regions of silenced chromatin.

Creative BioMart employs high-throughput screening to discover novel chemotypes that are capable of disrupting the interaction of histone with epigenetic reader protein chromodomain. Based on AlphaScreen technology, our robust, efficient and highly sensitive assay could measure the binding of chromodomain with peptide and assess potency of a large and chemically diverse compound collection.

Chromodomain Screening Assay at Creative BioMart

A convenient AlphaLISA format is applied to measure the inhibition of chromodomain binding to its substrate. Biotinylated peptide substrate, assay buffer, detection buffer and purified chromodomain-containing protein are required to perform the enzyme reaction, where the specific binding of chromodomain to the methylated-peptide substrate is critical. There are three steps performed on a microtiter plate. A sample containing chromodomain and an inhibitor to be tested is incubated with the biotinylated peptide substrate for one hour. Subsequently, acceptor beads and donor beads are added, followed by reading the Alpha-counts.

Figure 1. Procedure of chromodomain screening assay

Benefits of Our Services

1. A panel of assays available for inhibitors/targets screening
2. Select from IC₅₀ (half maximal inhibitory concentration) determination and single point concentrations
3. Fast feedback data after sample submission
4. Get proficient project guidance in a time-efficient manner

Supported by well-trained, knowledgeable team with years of drug research experience, Creative BioMart provides world-class chromodomain screening service to consistently deliver high-quality, efficient leading compounds to your development program of epigenetic therapy with minimized risks within the shortest timeline. Please contact us for more information and a detailed quote.

Reference
1. Simhadri, C.; et al. Chromodomain antagonists that target the polycomb-group methyllysine reader protein chromobox homolog 7 (CBX7). J Med Chem. 2014, 57(7): 2874–2883.