Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae.
Robert A ShepherdCody E EarpKristof B CankHuzefa A RajaJoanna E BurdetteSteven P MaherAdriana A MarinAnthony A RubertoSarah Lee MaiBlaise A DarveauxDennis E KyleCedric J PearceNicholas H OberlielsPublished in: The Journal of antibiotics (2023)
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 pEC 50 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 pCC 50 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.
Keyphrases
- plasmodium falciparum
- ms ms
- high throughput
- endothelial cells
- mass spectrometry
- magnetic resonance
- multiple sclerosis
- high resolution
- electronic health record
- induced pluripotent stem cells
- big data
- cell wall
- quality improvement
- solid state
- high resolution mass spectrometry
- machine learning
- artificial intelligence
- single cell