Molecular Design Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Bioorg Med Chem Lett. 2011 Jun 1;21(11):3335-41. doi: 10.1016/j.bmcl.2011.04.015. Epub 2011 Apr 8.
We describe the application of ligand based virtual screening technologies towards the discovery of novel plasmepsin (PM) inhibitors, a family of malarial parasitic aspartyl proteases. Pharmacophore queries were used to screen vendor libraries in search of active and selective compounds. The virtual hits were biologically assessed for activity and selectivity using whole cell Plasmodium falciparum parasites and on target in PM II, PM IV and the closely related human homologue, Cathepsin D assays. Here we report the virtual screening highlights, structures of the hits and their demonstrated biological activity.
我们描述了基于配体的虚拟筛选技术在新型疟原虫（Plasmodium）半胱氨酸蛋白酶（Plasmepsin，PM）抑制剂发现方面的应用，PM 是一类疟原虫寄生的天冬氨酸蛋白酶。基于药效基团的虚拟筛选技术被用来筛选供应商文库，以寻找活性和选择性化合物。使用全细胞恶性疟原虫寄生虫和针对 PM II、PM IV 以及密切相关的人类同源物组织蛋白酶 D 的测定法，对虚拟命中物的活性和选择性进行了生物评估。在这里，我们报告虚拟筛选的要点、命中物的结构及其表现出的生物活性。
