Chapter 6. Genetically Encoded SICLOPPS Libraries for the Identification of PPI Inhibitors

Genetically encoded cyclic peptide libraries have caused a step-change in hit discovery against some of the most challenging disease targets. Split-intein circular ligation of peptides and proteins (SICLOPPS) enables intracellular generation of cyclic peptide libraries in prokaryotes and eukaryotes. Library production in cells allows functional, cell-based screening for inhibitor identification. Here, we review the use of SICLOPPS screening for the identification of protein–protein interaction inhibitors against a variety of targets.