Tolypocladamides A-G: Cytotoxic Peptaibols from Tolypocladium inflatum.

ABSTRACT: Seven new peptaibols named tolypocladamides A-G have been isolated from an extract of the fungus Tolypocladium inflatum, which inhibits the interaction between Raf and oncogenic Ras in a cell-based high-throughput screening assay. Each peptaibol contains 11 amino acid residues, an octanoyl or decanoyl fatty acid chain at the N-terminus, and a leucinol moiety at the C-terminus. The peptaibol sequences were elucidated on the basis of 2D NMR and mass spectral fragmentation analyses. Amino acid configurations were determined by advanced Marfey's analyses. Tolypocladamides A-G caused significant inhibition of Ras/Raf interactions with IC₅₀ values ranging from 0.5 to 5.0 μM in a nanobioluminescence resonance energy transfer (NanoBRET) assay; however, no interactions were observ

SUBMITTER: Senadeera SPD 

PROVIDER: S-EPMC10616963 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature