title: TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093. Taxonomy, production, isolation, and biological activities.
abstract: In our course of screening for novel proteasome inhibitors, TMC-95A and its diastereomers, TMC-95B to D, were isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093. TMC-95A inhibited the chymotrypsin-like (ChT-L), trypsin-like (T-L), and peptidylglutamyl-peptide hydrolyzing (PGPH) activities of 20S proteasome with IC50 values of 5.4nM, 200nM, and 60nM, respectively. TMC-95B inhibited these activities to the same extent as TMC-95A, while the inhibitory activities of TMC-95C and D were 20 to 150 times weaker than that of TMC-95A and B. TMC-95A did not inhibit m-calpain, cathepsin L, and trypsin at 30 microM, suggesting its high selectivity for proteasome. Taxonomy of the producing strain is also described.
authors.affiliation: Department of Basic Technology, 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: M
authors.initials: M
authors.lastname: Nishio
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: T
authors.initials: T
authors.lastname: Ohnuki
authors.forename: S
authors.initials: S
authors.lastname: Komatsubara
mesh_terms: D002918:Chymotrypsin / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D005285:Fermentation; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D003904:Mitosporic Fungi / Q000145:classification* / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000187:drug effects*; D010455:Peptides / Q000378:metabolism; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D014357:Trypsin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D009097:Multienzyme Complexes; D010455:Peptides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C408291:TMC-95A; C408292:TMC-95B; C408293:TMC-95C; C408295:TMC-95D; D002918:Chymotrypsin; D014357:Trypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex