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

Authors
Type
Published Article
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Volume
134
Issue
18
Pages
7995–7999
Identifiers
DOI: 10.1021/ja302588v
Source
UCSC Aging biomedical-ucsc
License
Unknown

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.

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