Development of antimalarial drug targeting plasmodium falciparum dynamin

通过体外肌动蛋白聚合实验，我们确定了N‘-(4-二乙氨基)-4-甲氧基苯肼(DBHA)为动力蛋白抑制剂。此外，还研究了DBHA对褶皱形成和细胞迁移的影响，并将研究结果发表在一篇期刊文章中。恶性疟原虫中存在的动力蛋白亚型pfDy1和pfDy2在昆虫细胞中表达，并进行了纯化。利用这些重组蛋白，我们证明了pfDy1和pfDy2都具有GTP酶活性。研究还表明，pfDy1和pfDy2具有使脂膜变形的能力。此外，通过基于GTP酶活性分析的药物筛选确定了pfDy2抑制剂的候选分子。

By in vitro actin polymerization assay, we identified N'-(4-(diethylamino) benzylidene)-4-methoxybenzohydrazide (DBHA) as a dynamin inhibitor. Effects of DBHA on ruffle formation and cell migration were also examined, and the results on DBHA were published in a journal article.Dynamin isoforms present in plasmodium falciparum, pfDyn1 and pfDyn2, were expressed in insect cells, and they were purified. Using these recombinant proteins, we demonstrated that both pfDyn1 and pfDyn2 have GTPase activity. It was also shown that pfDyn1 and pfDyn2 have an ability to deform lipid membranes. Furthermore, pfDyn2 inhibitor candidate molecules were determined by GTPase activity assay-based drug screening.