Abstract

Epigenetic modifications regulate gene expression via
modifications to the chromatin that do not change the underlying DNA sequence.
These dynamic and reversible modifications include DNA methylation, histone
modification, and chromatin remodeling. The proteins involved in epigenetic modifications
can be categorized as writers, readers, or erasers. Writers covalently modify
chromatin, readers recognize these modifications, and erasers remove the
modifications. These epigenetic regulators play key roles in normal cellular
function, and abnormal expression or alterations leads to disease, such as
cancer and inflammation. Due to their role in disease, epigenetic modifiers are
attractive targets for the discovery and development of novel therapeutics.
Research in the field has shown many epigenetic proteins are druggable and
several FDA-approved drugs have already been developed (Ref. 1).

At Reaction Biology we offer a suite of services for
epigenetic drug discovery, including the largest panel for epigenetic screening
and profiling in the industry with over 30 Methyltransferases, 100+ Reader
Domain Proteins, HATs, HDACs, Demethylases, DUBs, PARPs, and more. In order to
directly probe the strength of the binding interaction between the epigenetic
target and potential therapeutics we offer biophysical assays, such as surface
plasmon resonance (SPR), isothermal titration calorimetry (ITC), and microscale
thermophoresis (MST). Here we present SPR binding data for three epigenetic
targets: NSD2 (writer), PRMT5 (writer), and Bromodomain-4 (reader). Through the
use of commercially available controls, we developed SPR assays for these
targets that can be used to screen compound or fragment libraries, determine
kinetics/affinity, and profile binding specificity.