Journal
ACS INFECTIOUS DISEASES
Volume 4, Issue 4, Pages 431-444Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.7b00197
Keywords
natural products; fragments; native mass spectrometry; target identification; malaria
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Funding
- Bill and Melinda Gates Foundation [OPP1035218]
- Australia Research Council (ARC) [LP120100485, LE20100170, LE0237908]
- National Health and Medical Research Council (NHMRC) [APP1046715]
- National Institutes of Health (NIH) [1P50 GM64655-01]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P50GM064655] Funding Source: NIH RePORTER
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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.
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