EPFL Team Builds Membrane-Permeable Cyclic Peptides From Scratch, Targeting a Core Barrier to Oral and Intracellular Peptide Drugs
A study from Christian Heinis's lab, published June 1 in Nature Chemical Biology, screened a library of 15,360 random cyclic peptides for the rare ability to cross cell membranes, then refined a lead (Peptide 30, 890.6 daltons) that blocked the intracellular Keap1-Nrf2 interaction in living cells. By engineering lower charge, fewer hydrogen-bond donors, and smaller polar surface area, the approach reaches targets inside cells without starting from a known ligand, a route toward peptide drugs that can be taken orally.