title: TMC-52A to D, novel cysteine proteinase inhibitors, produced by Gliocladium sp.
abstract: New cysteine proteinase inhibitors, TMC-52A, B, C, and D, were isolated from the fungal fermentation broth. On the basis of a taxonomical study, the producing strain, F-2665, was characterized as Gliocladium sp. Spectroscopic analyses and chemical degradation have shown TMC-52A to D to be epoxysuccinyl peptides. TMC-52A to D strongly inhibited cysteine proteinases, in particular, cathepsin L with IC50 values of 13 nM, 10nM, 10nM, and 6nM, respectively.
authors.affiliation: Lead Generation Research Laboratory at Toda, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Isshiki
authors.forename: M
authors.initials: M
authors.lastname: Nishio
authors.forename: N
authors.initials: N
authors.lastname: Sakurai
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: S
authors.initials: S
authors.lastname: Komatsubara
mesh_terms: D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010450:Endopeptidases; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D003904:Mitosporic Fungi / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D013386:Succinates; C114132:TMC 52A; C114133:TMC 52B; C114134:TMC 52C; C114135:TMC 52D; D014443:Tyrosine; D010649:Phenylalanine; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L