Work

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

Year: 2012

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja302588v

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

Institution: California Institute of Technology

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of General Medical Sciences

Awards: The role of miR-155 in cell cycle regulation and tumorigenesis, Regulation of Gene Expression by DNA Binding Ligands, G5347587813, DNA-binding polyamides as Hedgehog inhibitors in human carcinoma