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 IC(50) value of 96 nM, while scytonemide B was inactive at 50 μM.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, United States.
Aleksej
A
Krunic
Armelle
A
Vallat
Shunyan
S
Mo
Daniel D
DD
Lantvit
Steven M
SM
Swanson
Jimmy
J
Orjala
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002210:Caprylates / Q000737:chemistry; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D061988:Proteasome Inhibitors
D000970:Antineoplastic Agents; D002210:Caprylates; D047630:Depsipeptides; D061988:Proteasome Inhibitors; C554485:scytonemide A; C554486:scytonemide B; C101940:3-hydroxyoctanoic acid