De Novo Cyclic Peptides: A RaPID Approach to Chemical Tool Development

mRNA-display based cyclic peptide discovery platforms provide powerful routes to rapidly identify tight binding ligands to almost any target of choice. The addition of genetic code reprogramming allows the introduction of non-native chemistries and associated new functionalities into peptide hits.

In this talk, I will describe recent work from our group to modify mRNA-display strategies to expand their target scope and apply these to a range of epigenetic protein targets. Initially, I will discuss recent work in which we expand the target scope of peptide screens by screening proteins in a lysate context. I will then describe our work to identify chemical probes with diverse functions against PADI4, an arginine deiminase linked to the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. Finally, I will introduce our recent development of photocrosslinking-RaPID (XL-RaPID) a strategy to accelerate discovery of cyclic peptides that photocrosslink to a target of interest and its further extension to electrophilic cyclic peptide discovery.

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Contacts: Lianne Willems lianne.willems@york.ac.uk and Chris Spicer chris.spicer@york.ac.uk.