1999 Volume 52 Issue 12 Pages 1069-1076
TMC-86A, B and TMC-96, new 20S proteasome inhibitors with an epoxy-β-aminoketone moiety, were isolated from the fermentation broth of Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094, respectively. TMC-86A, B and TMC-96 inhibited the chymotrypsin-like and peptidylglutamyl-peptide hydrolyzing activities of 20S proteasome with the following IC50 values: TMC-86A, 5.1 μM and 3.7 μM; TMC-86B, 1.1 μM and 31 μM; TMC96, 2.9 μM and 3.5μM, respectively. TMC-86A, B and TMC-96 exhibited the weak inhibitory activity against the trypsin-like activity of 20S proteasome with IC50 values of 51 μM, 250μM, and 36μM, respectively. They did not inhibit m-calpain, cathepsin L, and trypsin at 100 μM, suggesting their high specificity for proteasome. Taxonomy of the producing strains is also described.
