一种用于炭疽致死因子抑制的高通量筛选方法。
A high-throughput screening approach to anthrax lethal factor inhibition.
作者信息
Johnson Sherida L, Chen Li-Hsing, Pellecchia Maurizio
机构信息
Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
出版信息
Bioorg Chem. 2007 Aug;35(4):306-12. doi: 10.1016/j.bioorg.2006.12.005. Epub 2007 Feb 22.
Abstract
A high-throughput screening approach was used to identify new inhibitors of the metallo-protease lethal factor from Bacillus anthracis. A library of approximately 14,000 compounds was screened using a fluorescence-based in vitro assay and hits were further characterized enzymatically via measurements of IC50 and Ki values against a small panel of metallo-proteases. This study led to the identification of new scaffolds that inhibit LF and the Botulinum Neurotoxin Type A in the low micromolar range, while sparing the human metallo-proteases MMP-2 and MMP-9. Therefore, these scaffolds could be further exploited for the development of potent and selective anti-toxin agents.
摘要
采用高通量筛选方法来鉴定炭疽芽孢杆菌金属蛋白酶致死因子的新型抑制剂。使用基于荧光的体外测定法对约14000种化合物的文库进行筛选，并通过针对一小部分金属蛋白酶测量IC50和Ki值，对筛选出的活性物质进行进一步的酶学表征。这项研究导致鉴定出在低微摩尔范围内抑制致死因子和A型肉毒杆菌神经毒素的新型骨架，同时不影响人类金属蛋白酶MMP - 2和MMP - 9。因此，这些骨架可进一步用于开发强效和选择性抗毒素药物。
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