Monday, 20 June 4:00pm – 5:00pm

This seminar will be delivered in Chemistry Lecture Theatre 2 and Online Zoom Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Dr Beatrice Chiew; School of Environmental and Life Sciences, University of Newcastle

Host: Dr Jonathan Danon

Title: Design in the dark – illuminating the druggability of 53BP1 for BRCA-1 breast cancer

Abstract: Fragment-Based drug discovery (FBDD) is an established means of drug discovery where small, low complexity chemical compounds with weak binding affinity to drug targets are grown into drug-like molecules. This approach offers advantages over traditional High throughput screening (HTS) campaigns such as saving experimental costs and offering diverse hits. A key concession of FBDD is that initial hits tend to display weak binding to protein targets, and that structural data is heavily relied upon to develop these hits to higher affinity.

REFiL (Rapid Elaboration of Fragments into Leads) is a workflow designed to develop chemical probes without need of structural data. This workflow utilizes microscale parallel synthesis and Off-rate screening by Surface Plasmon Resonance to expedite the production of lead-like compounds to establish the druggability of a protein of interest. This workflow was applied to the DNA reader protein 53BP1 to identify compounds for use against BRCA-1 breast cancer. This workflow has enabled the development of 4 small molecule 53BP1 binders that are equipotent to the histone binding partner.

Biography: Beatrice completed a pharmaceutical science bachelor’s degree at the Monash Institute of Pharmaceutical Sciences (MIPS) in Melbourne majoring in Medicinal Chemistry. She then went on to do her honours and PhD under the supervision of Prof. Martin Scanlon and Dr. Bradley Doak in the field of Fragment Based Drug discovery. In her honours year she utilised fragment linking to identify potent binders of HIV integrase, and through her PhD research, she worked on a novel structure-agnostic means of fragment elaboration against the epigenetic reader protein 53BP1. Beatrice is currently working with Prof. Adam McCluskey at the University of Newcastle on developing novel Dynamin chemical probes. In her spare time Beatrice is an avid sketcher/painter and hip-hop dancer.