NucleoBeads™

DNA-binding proteins, especially transcription factors, act as major oncodrivers and represent an important therapeutic target class. NucleoBeads™ is a quantitative chemical proteomics technique that enables comprehensive profiling of proteins that selectively bind specific nucleotide sequences (DNA or RNA). Our approach leverages a proprietary mix of double-strand DNA oligonucleotide probes and quantitative proteomics to reproducibly quantify almost 400 transcription factors and complexes – including P53, MYC:MAX, NFkB, JUN, TEAD, and more – in a single experiment from cell or tissue extracts. This technology identifies both physical and functional inhibitors of DNA binding and modulators of transcription factor activity. NucleoBeads™-bound proteins can be competed by compounds or free nucleotide sequences in a competition binding assay format to uncover their molecular (off-)targets and to determine affinity and selectivity values.

Due to its high-throughput capabilities, this technology is well suited to screen large compound libraries. While assays like ChIP-seq can be confounded by indirect effects of drug treatment, NucleoBeads™ enables direct monitoring of DNA-binding interactions and their drug-induced disruption. In addition to being readily adaptable to new transcription factor classes, the NucleoBeads™ platform is compatible with other nucleotide modalities, such as RNA and custom-designed oligonucleotides, enabling the study of RNA-binding proteins and nucleic acid interactions beyond DNA.