Vu Hoan, Pedro Liliana, Mak Tin, McCormick Brendan, Rowley Jessica, Liu Miaomiao, Di Capua Angela, Williams-Noonan Billy, Pham Ngoc B, Pouwer Rebecca, Nguyen Bao, Andrews Katherine T, Skinner-Adams Tina, Kim Jessica, Hol Wim G J, Hui Raymond, Crowther Gregory J, Van Voorhis Wesley C, Quinn Ronald J
Griffith Institute for Drug Discovery , Griffith University , 170 Kessels Road , Nathan , Queensland 4111 , Australia.
Structural Genomics Consortium , University of Toronto , MaRS South Tower, seventh floor 101 College Street , Toronto , Ontario M5G 1L7 , Canada.
ACS Infect Dis. 2018 Apr 13;4(4):431-444. doi: 10.1021/acsinfecdis.7b00197. Epub 2018 Mar 3.
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.
天然产物以其生物学相关性、高度的三维性以及对大量未开发化学空间区域的可及性而闻名。为了在后基因组时代塑造我们对天然产物与蛋白质靶点之间相互作用的理解，我们使用了天然质谱法，利用基于天然产物的片段库研究了62个潜在的疟疾蛋白质靶点。我们在此揭示了96种低分子量天然产物，它们被鉴定为32个假定疟疾靶点的结合伴侣。79个片段在对恶性疟原虫具有直接生长抑制作用的浓度下，有望开发针对这些蛋白质靶点的片段命中物。这为公共领域已发表的高通量筛选活性库增添了一个片段库。
