Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Huzefa A. Raja, Research Scientist (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey’s method. In an in vitro assay for antimalarial potency, 1 displayed a pEC50 value of 5.75?±?0.49 against malaria-causing Plasmodium falciparum. Compound 1 was also tested in a counter screen for general cytotoxicity against human hepatocellular carcinoma (HepG2), yielding a pCC50 value of 5.01?±?0.45 and indicating a selectivity factor of ~6. This makes 1 the third known cyclic pentapeptide biosynthesized by fungi with antimalarial activity.

Additional Information

Publication
Shepherd, R.A., Earp, C.E., Cank, K.B., Raja, H.A., Burdette, J., Maher, S.P., Marin, A.A., Ruberto, A.A., Mai, S.L., Darveaux, B.A., Kyle, D.E. 2023. Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae. The Journal of Antibiotics 76: 642–649.
Language: English
Date: 2023
Keywords
sheptide, cyclic pentapeptide, Herpotrichiellaceae, fungal strain

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