Pharmacokinetics of Py-Im Polyamides Depend on Architecture: Cyclic versus Linear

Creators: Raskatov, Jevgenij A.; Hargrove, Amanda E.; So, Alex Y.; Dervan, Peter B.

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.

Additional Information

© 2012 American Chemical Society. Received: March 16, 2012; Published: April 17, 2012. J.A.R. is grateful to the Alexander von Humboldt foundation for the award of a Feodor Lynen postdoctoral fellowship. A.E.H. thanks the California Tobacco-Related Disease Research Program (19FT-0105) and the NIH (NRSA number 1F32CA156833) for postdoctoral support. A.Y.S. acknowledges the NIH for postdoctoral funding (NRSA number 5F32CA139883). We are grateful for support by The Ellison Medical Foundation (AG-SS-2256-09) and the National Institutes of Health (GM051747). The authors declare no competing financial interest.

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Accepted Version - nihms372939.pdf

Supplemental Material - ja302588v_si_001.pdf

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