Pharmacokinetics of Py-Im polyamides depend on architecture: cyclic versus linear.

Authors :: Raskatov JA
Hargrove AE
So AY
Dervan PB
Source :: Journal of the American Chemical Society [J Am Chem Soc] 2012 May 09; Vol. 134 (18), pp. 7995-9. Date of Electronic Publication: 2012 Apr 24.
Publication Year :: 2012
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.

Subjects :: Animals
Body Weight drug effects
Imidazoles adverse effects
Mice
Mice, Inbred C57BL
Nylons adverse effects
Pyrroles adverse effects
Imidazoles chemistry
Imidazoles pharmacokinetics
Nylons chemistry
Nylons pharmacokinetics
Pyrroles chemistry
Pyrroles pharmacokinetics

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