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The Antimalarial Natural Product Symplostatin 4 Is a Nanomolar Inhibitor of the Food Vacuole Falcipains
Authors:Sara Christina Stolze  Edgar Deu  Farnusch Kaschani  Nan Li  Bogdan I Florea  Kerstin H Richau  Tom Colby  Renier AL van der Hoorn  Hermen S Overkleeft  Matthew Bogyo  Markus Kaiser
Institution:1. Zentrum für Medizinische Biotechnologie, Fakultät für Biologie, Universität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany;2. Department of Pathology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA;3. Max Planck Institute for Plant Breeding Research, Carl-von-Linné-Weg 10, 50829 Cologne, Germany;4. Faculty of Science, Leiden Institute of Chemistry, Bio-organic Synthesis, Gorlaeus Laboratories, Einsteinweg 55, 2333 CC Leiden, The Netherlands
Abstract:
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  • Highlights? A convergent chemical synthesis of symplostatin 4 (Sym4) and Sym4 derivatives is reported ? Sym4 irreversibly inhibits malarial falcipains in infected red blood cells ? Sym4's unusual methyl-methoxypyrrolinone group is required for nanomolar inhibition of falcipains
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