Peptide display involves the screening of large combinatorial peptide libraries which are barcoded by their encoding DNA sequence, enabling the identification of potent binders for any therapeutic target of interest. However, converting these peptide binders into genuine therapeutic leads is often a challenging process, due to the sub-optimal pharmacokinetic properties of typical screening hits.
We have adapted mRNA display and phage display workflows to generate non-canonical peptide hits that can facilitate downstream hit-to-lead optimisation.
In this talk, I will present one of our mRNA display campaigns against telomeric cancer targets, where incorporation of fragment-bearing amino acids enables the elucidation of bound structures to guide SAR studies. I will also discuss a phage display campaign against a regulator of telomerase assembly, where using simple cysteine-containing libraries leads to the identification of novel covalent inhibitors.