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Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

2018; American Chemical Society; Volume: 4; Issue: 4 Linguagem: Inglês

10.1021/acsinfecdis.7b00197

2373-8227

Hoan Vu, Liliana Pedro, Tin Mak, B. P. McCormick, Jessica A. Rowley, Miaomiao Liu, Angela Di Capua, Billy J. Williams‐Noonan, Ngoc B. Pham, Rebecca H. Pouwer, Bao Nguyen, Katherine T. Andrews, Tina S. Skinner‐Adams, Jessica Kim, Wim G. J. Hol, Raymond Hui, Gregory J. Crowther, Wesley C. Van Voorhis, Ronald J. Quinn,

Chemical Synthesis and Analysis

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.