De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries

Cellular selection has emerged as a powerful approach for high throughput de novo discovery of bioactive cyclic peptides (CPs). This strategy coexpresses genetically encoded CP libraries with the target of interest in cells and uses customizable selection systems to link desired CP activities to a selectable phenotype to directly identify functional inhibitors. Cellular selections have yielded many CP inhibitors against a diverse range of therapeutic targets and have been continuously empowered by expansions in the CP diversity and selection repertoire. In this review, we summarize studies on cellular selection using genetically encoded CP libraries and discuss opportunities for future application of this technology.