title: TMC-86A, B and TMC-96, new proteasome inhibitors from Streptomyces sp. TC 1084 and Saccharothrix sp. TC 1094. I. Taxonomy, fermentation, isolation, and biological activities.
abstract: TMC-86A, B and TMC-96, new 20S proteasome inhibitors with an epoxy-beta-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 microM and 3.7microM; TMC-86B, 1.1 microM and 31 microM; TMC-96, 2.9 microM and 3.5 microM, 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 microM, 250 microM, and 36 microM, respectively. They did not inhibit m-calpain, cathepsin L, and trypsin at 100 microM, suggesting their high specificity for proteasome. Taxonomy of the producing strains is also described.
authors.affiliation: Basic Technology Department, TAnabe Seiyaku Co., Ltd., Toda-shi, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koguchi
authors.forename: J
authors.initials: J
authors.lastname: Kohno
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Nishio
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Ohnuki
authors.forename: S
authors.initials: S
authors.lastname: Komatsubara
mesh_terms: D000192:Actinomycetales / Q000378:metabolism*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D004151:Dipeptides / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D051379:Mice; D009097:Multienzyme Complexes / Q000187:drug effects*; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*
chemical_list: D004151:Dipeptides; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; C405050:TMC 86A; C405051:TMC 86B; C405052:TMC 96; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex