Diverse Modes of Targeting BET family proteins with Cyclic Peptides

DRA lecture held by Louise Walport, Senior Lecturer, Francis Crick Institute, London, United Kingdom

mRNA-display based cyclic peptide discovery platforms provide powerful routes to rapidly identify tight binding ligands to a wide range of protein targets. In this talk, I will describe recent work from our group developing cyclic peptide binders of the BET family proteins and general principles we have learned from this work. Initially I will discuss our work with individual acetyl lysine binding bromodomains from these proteins, which revealed how diverse peptide secondary structures can bind to single protein interfaces and how binding selectivity can be derived from sites distal sites to the binding site. I will go on to discuss how we have modified our peptide selection approach to allow identification of covalent peptide binders that bind alternate bromodomain surfaces. Finally, I will share recent work in which we expand the RaPID target scope by screening proteins in a lysate context. This has allowed us to identify peptide binders to other domains of the BET family members.

The lecture is organised on behalf of the graduate programme in pharmaceutical sciences, Drug Research Academy, by Associate Professor Joseph Rogers, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen.

The DRA lecture is free of charge and open for attendance by all interested parties. It is not necessary to pre-register.