Investigation of the Relative Cellular Permeability of DNA-Binding Pyrrole−Imidazole Polyamides

Pyrrole−imidazole (Py-Im) polyamides are a group of chemicals that are able to bind specifically to DNA sequences in vitro and in mammalian cells. Using a cell based reporter assay, we investigated the size and linker affects on the cellular permeability of polyamides. We found that the conventional β-alanine-3,3′-diamino-N-methyldipropylamine (βDa) linker strongly limited the cellular permeability. We discovered that a short ethylene diamine (Et) linker displayed high cellular permeability. With the improved Et linker, we found that the cellular permeability of polyamides was size-dependent.