Scytonemides A and B, Cyclic Peptides with 20S Proteasome Inhibitory Activity from the Cultured Cyanobacterium Scytonema hofmanii

Two cyclic peptides, scytonemides A (1) and B (2), were isolated from the cultured fresh water cyanobacterium Scytonema hofmannii (UTEX 1834) by bioassay-guided fractionation using a proteasome inhibition assay. The planar structures of the compounds were determined by a combination of MS and 1D and 2D NMR spectroscopy. The advanced Marfey's method was used to determine the absolute configuration of both peptides. Scytonemide A possesses an unusual imino linkage, while scytonemide B is a depsipeptide containing 3-hydroxyoctanoic acid in the macrocycle. Both isolates were evaluated for their inhibition of the 20S proteasome, and scytonemide A displayed an IC50 value of 96 nM, while scytonemide B was inactive at 50 mu M.