Fragment-Based Identification of Ligands for Bromodomain-Containing Factor 3 of .

The () parasite is the cause of Chagas disease, a neglected disease endemic in South America. The life cycle of the parasite is complex and includes transitions between distinct life stages. This change in phenotype (without a change in genotype) could be controlled by epigenetic regulation, and might involve the bromodomain-containing factors 1-5 (BDF1-5). However, little is known about the function of the BDF1-5. Here we describe a fragment-based approach to identify ligands for bromodomain-containing factor 3 (BDF3). We expressed a soluble construct of BDF3 in , and used this to develop a range of biophysical assays for this protein. Fragment screening identified 12 compounds that bind to the BDF3 bromodomain. On the basis of this screen, we developed functional ligands containing a fluorescence or F reporter group, and a photo-crosslinking probe for BDF3. These tool compounds will be invaluable in future studies on the function of BDF3 and will provide insight into the biology of .