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.
A Nature Chemical Biology paper published May 2026 reported TerminaTOR, a genetically encoded peptide inhibitor of mTORC1 that can be targeted to specific subcellular locations and used to dissect mTORC1 biology in living cells. Targeted to the lysosome, TerminaTOR inhibits canonical lysosomal mTORC1 and induces autophagy — recapitulating rapamycin's pharmacology. Targeted to the nucleus, TerminaTOR specifically inhibits nuclear mTORC1 and reveals a previously uncharacterized regulatory function: nuclear mTORC1 controls transcription of CCAAT-motif-containing genes and promotes cancer cell proliferation. The work creates a tool for spatially separating canonical (cytoplasmic) and noncanonical (nuclear) mTORC1 functions and identifies nuclear mTORC1 as a potentially druggable axis distinct from the lysosomal pathway. Therapeutic implication: cancer programs targeting mTORC1 might benefit from nucleus-selective inhibitors that spare lysosomal autophagy.