These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
submitted on 31.08.2020 and posted on 03.09.2020by Corentine Laurin, Joseph Bluck, Anthony Chan, Michelle Keller, Andrew Boczek, Amy Scorah, K. F. Larissa See, Laura Jennings, David Hewings, Fern Woodhouse, Matthias Schiedel, Philip Humphreys, Philip Biggin, Stuart Conway
The Trypanosoma cruzi (T. cruzi) parasite is the cause of Chagas disease, a neglected disease endemic in South America. The life cycle of the T. cruzi 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 (TcBDF1-5). However, little is known about the function of the TcBDF1-5. Here we describe a fragment-based approach to identify ligands for T. cruzi bromodomain-containing factor 3 (TcBDF3). We expressed a soluble construct of TcBDF3 in E. coli, and used this to develop a range of biophysical assays for this protein. Fragment screening identified twelve compounds that bind to the TcBDF3 bromodomain. Based on this screen, we developed functional ligands containing a fluorescence or 19F reporter group, and a photo-crosslinking probe for TcBDF3. These tools compounds will be invaluable in future studies on the function of TcBDF3 and will provide insight into the biology of T. cruzi.