Pharmacokinetics of Py-Im Polyamides Depend on Architecture: Cyclic versus Linear
Pharmacokinetics of Py-Im Polyamides Depend on Architecture: Cyclic versus Linear
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DOI：
10.1021/ja302588v
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发表时间：
2012-05-09
影响因子：
15
通讯作者：
Dervan, Peter B.
中科院分区：
文献类型：
--
作者：
Raskatov, Jevgenij A.;Hargrove, Amanda E.;Dervan, Peter B.
研究了3种大小、含量相近但形状不同的吡咯-咪唑聚酰胺在小鼠体内的药动学特性。值得注意的是，为相同DNA序列编程的发夹和环状低聚物5‘-WGGWWW-3’显示出不同的药代动力学特性。此外，发夹1和周期2表现出截然不同的动物毒性。这些数据为设计DNA结合的Py-Im聚酰胺进行体内测试提供了基础。
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.