Massive barcode-free chemical screenings enable the discovery of bioactive macrocycles with passive membrane permeability ino.to/IwMIfRQ
Synthetic macrocycles are promising therapeutics; however, most high-throughput discovery platforms rely on genetically encoded libraries of large peptide macrocycles, which are typically not optimized for drug-like properties. Here, the authors report CycloSEL (Cyclic Self-Encoded Libraries), an end-to-end workflow that screens synthetic macrocycle libraries enriched in drug-like ‘beyond rule of five’ features, based on affinity selections and hit identification by tandem mass spectrometry.
