Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
Guetzoyan L., Ingham RJ., Nikbin N., Rossignol J., Wolling M., Baumert M., Burgess-Brown NA., Strain-Damerell CM., Shrestha L., Brennan PE., Fedorov O., Knapp S., Ley SV.
A combination of conventional organic synthesis, remotely monitored flow synthesis and bioassay platforms, were used for the evaluation of novel inhibitors targeting bromodomains outside the well-studied bromodomain and extra terminal (BET) family, here exemplified by activity measurements on the bromodomain of BRD9 protein, a component of some tissue-specific SWi/SNF chromatin remodelling complexes. The Frontal Affinity Chromatography combined with Mass Spectrometry (FAC-MS) method proved to be reliable and results correlated well with an independent thermal shift assay. © 2014 the Partner Organisations.