Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 134, Issue 18, Pages 7995-7999Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja302588v
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Funding
- Alexander von Humboldt foundation
- California Tobacco-Related Disease Research Program [19FT-0105]
- NIH (NRSA) [1F32CA156833, 5F32CA139883]
- Ellison Medical Foundation [AG-SS-2256-09]
- National Institutes of Health [GM051747]
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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.
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