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Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.
ACS Infectious Diseases ( IF 5.3 ) Pub Date : 2018-03-03 , DOI: 10.1021/acsinfecdis.7b00197
Hoan Vu 1 , Liliana Pedro 1 , Tin Mak 1 , Brendan McCormick 1 , Jessica Rowley 1 , Miaomiao Liu 1 , Angela Di Capua 1 , Billy Williams-Noonan 1 , Ngoc B Pham 1 , Rebecca Pouwer 1 , Bao Nguyen 1 , Katherine T Andrews 1 , Tina Skinner-Adams 1 , Jessica Kim , Wim G J Hol , Raymond Hui 2 , Gregory J Crowther , Wesley C Van Voorhis , Ronald J Quinn 1
Affiliation  

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

中文翻译:

天然产物库的基于片段的筛选,针对使用天然质谱的62种潜在疟疾药物靶标。

天然产物以其生物学相关性,高度的三维性和进入很大程度上未开发的化学空间区域而闻名。为了塑造我们对后基因组时代天然产物与蛋白质靶标之间相互作用的理解,我们使用了天然质谱技术,使用基于天然产物的片段库研究了62种潜在的疟疾蛋白质靶标。我们在这里揭示了96种低分子量天然产物,它们被确定为32种疟疾靶标的结合伴侣。七十九(79)个片段对恶性疟原虫具有一定的直接生长抑制作用,其浓度有望促进针对这些蛋白质靶标的片段命中。这会将片段库添加到公共领域中已发布的HTS活动库中。
更新日期:2018-02-13
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