Abstract 1933 Small molecule analysis of UHRF2 using fluorescence polarization

UHRF1(Ubiquitin Like With PHD and Ring Finger Domains 1) and UHRF2 are epigenetic proteins that regulate histone modifications and DNA methylation. Both proteins contain TTD(Tandem Tudor Domain) and PHD(Plant Homeodomain) that bind to histone H3 trimethylated at lysine 9(H3K9Me3). Both UHRF1 and UHRF2 have been implicated in various cancers(Breast, Cervical, Pancreatic, Prostate, Lung, and Gliomas), thus drugs that can selectively target these proteins are attractive anti-cancer therapies. Previous studies have identified multiple small molecule drugs that interrupt UHRF1's TTD-PHD ability to bind to histone H3, however, the same molecules have yet to be tested on UHRF2. The purpose of this study was to test the ability of various molecules to disrupt the histone binding properties of UHRF2 TTD-PHD. Using fluorescence polarization, we performed competition experiments with these molecules against UHRF2 bound to an H3 peptide to measure their relative binding affinities. We acknowledge Eastern Michigan University internal funding awards.