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Journal of Biomolecular Screening
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Development of a Plasmepsin II Fluorescence Polarization Assay Suitable for High Throughput Antimalarial Drug Discovery

Horst Flotow

Merlion Pharmaceuticals Pte. Ltd., The Fleming, Singapore

Chung-Yan Leong

Merlion Pharmaceuticals Pte. Ltd., The Fleming, Singapore

Antony D. Buss

Merlion Pharmaceuticals Pte. Ltd., The Fleming, Singapore

Despite decades of research, malaria remains the world's most deadly parasitic disease. New treatments with novel mechanisms of action are urgently needed. Plasmepsin II is an aspartyl protease that has been validated as an antimalarial therapeutic target enzyme. Although natural products form the basis of most modern antimalarial drugs, no systematic high-throughput screening has been reported against this target. We have designed an effective strategy for carrying out high-throughput screening of an extensive library of natural products that uses a fluorescence resonance energy transfer primary screening assay in tandem with a fluorescence polarization assay. This strategy allows rapid screening of the library coupled with effective discrimination and elimination of false-positive samples and selection of true hits for chemical isolation of inhibitors of plasmepsin II.

Journal of Biomolecular Screening, Vol. 7, No. 4, 367-371 (2002)
DOI: 10.1177/108705710200700409
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