Department of Medicinal Chemistry, Emerging Field Pharmacoinformatics, University of Vienna, Althanstrasse 14, 1090 Wien, Austria.
ChemMedChem. 2010 Mar 1;5(3):436-42. doi: 10.1002/cmdc.200900374.
The inner cavity of the hERG potassium ion channel can accommodate large, structurally diverse compounds that can be trapped in the channel by closure of the activation gate. A small set of propafenone derivatives was synthesized, and both use-dependency and recovery from block were tested in order to gain insight into the behavior of these compounds with respect to trapping and non-trapping. Ligand-protein docking into homology models of the closed and open state of the hERG channel provides the first evidence for the molecular basis of drug trapping.
hERG 钾离子通道的内腔可容纳结构多样的大型化合物，这些化合物可通过激活门的关闭而滞留在通道中。合成了一小组普罗帕酮衍生物，并测试了它们的使用依赖性和阻断恢复情况，以深入了解这些化合物在捕获和非捕获方面的行为。将配体-蛋白对接入 hERG 通道的闭孔和开孔同源模型中，为药物捕获的分子基础提供了首个证据。
