Achieving cell penetration with distance-matching cysteine cross-linkers: a facile route to cell-permeable peptide dual inhibitors of Mdm2/Mdmx

We report the design of bisarylmethylene bromides as a new class of rigid, distance-matching cysteine cross-linkers. By cross-linking a peptide dual inhibitor of Mdm2/Mdmx containing cysteines at i,i+7 positions, dramatic enhancement in cell permeability was achieved, along with increased helicity and biological activity.