Louise Walport
Group Leader
The Francis Crick Institute
UK
Louise obtained her PhD in chemical biology from the University of Oxford in 2014 under the supervision of Prof. Chris Schofield and Prof. Christina Redfield. She used a combination of biochemical and structural techniques to study the structure and function of ‘reader’ and ‘eraser’ proteins involved in epigenetics.
Following further postdoctoral work in Oxford, she obtained a Global Marie Skłodowska-Curie Fellowship to work in Japan for two years in the laboratory of Hiroaki Suga at the University of Tokyo, with a return year in Chris Schofield’s laboratory at the University of Oxford. In 2018, she established her lab at the Francis Crick Institute in a joint appointment with the Chemistry Department at Imperial College London.
L03 - Expanding the Functionality of De Novo Cyclic Peptides
mRNA-display based cyclic peptide discovery platforms provide powerful routes to rapidly identify tight binding hits to almost any target of choice. Genetic code reprogramming strategies permit wider chemical space to be covered through incorporation of non-canonical amino acids. In this talk I will describe recent work from my group expanding the functionality that can be encoded in cyclic peptide libraries, including through introduction of light responsive functional groups. I will discuss our recent efforts to develop a novel mRNA display strategy, photocrosslinking-RaPID (XL-RaPID), and exploit its ability to accelerate the discovery of cyclic peptides that photocrosslink to a target of interest. As a proof of concept, we generated a benzophenone-containing library and applied XL-RaPID screening against a model target, the second bromodomain of BRD3. Our crosslinking screening resulted in two optimal candidates that selectively labelled the target protein in cell lysate. Overall, our work introduces direct photocrosslinking screening as a versatile technique for identifying covalent peptide ligands from mRNA display libraries incorporating reactive warheads.
L. J. Walport
Department of Chemistry, Imperial College London, London, SW7 2AZ
The Francis Crick Institute, 1 Midland Road, London, NW1 1AT