title: Pharmacokinetics of Py-Im polyamides depend on architecture: cyclic versus linear.
abstract: The pharmacokinetic properties of three pyrrole-imidazole (Py-Im) polyamides of similar size and Py-Im content but different shape were studied in the mouse. Remarkably, hairpin and cyclic oligomers programmed for the same DNA sequence 5'-WGGWWW-3' displayed distinct pharmacokinetic properties. Furthermore, the hairpin 1 and cycle 2 exhibited vastly different animal toxicities. These data provide a foundation for design of DNA binding Py-Im polyamides to be tested in vivo.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Jevgenij A
authors.initials: JA
authors.lastname: Raskatov
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Hargrove
authors.forename: Alex Y
authors.initials: AY
authors.lastname: So
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D007093:Imidazoles / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009757:Nylons / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles