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 beta-alanine-3,3'-diamino-N-methyldipropylamine (betaDa) 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.
Liu
Bo
B
Department of Internal Medicine, Division of Translational Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Kodadek
Thomas
T
D004247:DNA / Q000378:metabolism*; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics*; D009757:Nylons / Q000493:pharmacokinetics*; D010539:Permeability; D011758:Pyrroles / Q000493:pharmacokinetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013329:Structure-Activity Relationship
D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D004247:DNA