首个低微摩尔浓度 SecA 抑制剂。
The first low microM SecA inhibitors.
机构信息
Department of Chemistry, Georgia State University, Atlanta, GA 30302-4098, USA.
出版信息
Bioorg Med Chem. 2010 Feb 15;18(4):1617-25. doi: 10.1016/j.bmc.2009.12.074. Epub 2010 Jan 6.
Abstract
SecA ATPase is a critical member of the Sec family, which is important in the translocation of membrane and secreted polypeptides/proteins in bacteria. Small molecule inhibitors can be very useful research tools as well as leads for future antimicrobial agent development. Based on previous virtual screening work, we optimized the structures of two hit compounds and obtained SecA ATPase inhibitors with IC(50) in the single digit micromolar range. These represent the first low micromolar synthetic inhibitors of bacterial SecA and will be very useful for mechanistic studies.
摘要
SecA ATP 酶是 Sec 家族的关键成员，在细菌中跨膜和分泌多肽/蛋白质的易位中起着重要作用。小分子抑制剂不仅是非常有用的研究工具，也是未来抗菌药物开发的先导化合物。基于之前的虚拟筛选工作，我们对两个命中化合物的结构进行了优化，得到了 IC50 在个位数微摩尔范围内的 SecA ATP 酶抑制剂。这些是第一个低微摩尔的细菌 SecA 合成抑制剂，对于机制研究将非常有用。
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