Acidiphilamides A-E, Modified Peptides as Autophagy Inhibitors from an Acidophilic Actinobacterium, Streptacidiphilus rugosus.
Sunghoon HwangYejin YunWon Hoon ChoiSeung Bum KimJongheon ShinMin Jae LeeDong-Chan OhPublished in: Journal of natural products (2019)
Five new tripeptides, acidiphilamides A-E (1-5), were discovered along with two previously reported compounds, l-isoleucinamide (6) and l-valinamide (7), from Streptacidiphilus rugosus AM-16, an acidophilic actinobacterial strain isolated from acidic forest soil. The structures of 1-5 were elucidated as modified tripeptides bearing phenylalaninol or methioninol fragments with C3-C5 acyl chains based mainly on NMR and mass spectroscopic data. The absolute configurations of the amine units were established by advanced Marfey's method and GITC (2,3,4,6-tetra- O-acetyl-β-d-glucopyranosyl isothiocyanate) derivatization followed by LC/MS analysis. Acidiphilamides A and B (1 and 2), the first secondary metabolites isolated from the rare actinobacterial genus Streptacidiphilus, significantly inhibited autophagic flux but not proteasome activity in HeLa cells. These compounds appeared to block mainly the autophagosome-lysosome fusion step in the late stage of cellular autophagy.
Keyphrases
- cell death
- cell cycle arrest
- induced apoptosis
- endoplasmic reticulum stress
- ms ms
- high resolution
- signaling pathway
- oxidative stress
- magnetic resonance
- climate change
- molecular docking
- electronic health record
- pi k akt
- fluorescent probe
- gas chromatography mass spectrometry
- liquid chromatography
- simultaneous determination
- solid state
- ionic liquid
- cell proliferation
- mass spectrometry
- data analysis
- amino acid
- fatty acid
- solid phase extraction
- molecular dynamics simulations