title: Isolation, structure elucidation, and total synthesis of tryptopeptins A and B, new TGF-β signaling modulators from Streptomyces sp.
abstract: Two new microbial metabolites, tryptopeptins A (1) and B (2), were isolated from the cultured broth of Streptomyces sp. KUSC-G11, as modulators of the transforming growth factor-β (TGF-β) signaling pathway. Their chemical structures consisting of isovalerate, N-Me-L-Val, L-allo-Thr, and a tryptophan-related residue were elucidated on the basis of spectroscopic analyses, while they were unambiguously determined by total syntheses. A structure-activity relationship (SAR) study using natural and synthesized tryptopeptins revealed the importance of the α,β-epoxyketone function located at the C terminus. These new TGF-β signaling modulators would be highly useful for development of new drug leads targeting TGF-β-related diseases such as fibrosis and cancer.
authors.affiliation: Department of System Chemotherapy and Molecular Sciences and §Department of Bioorganic Medicinal Chemistry & Chemogenomics, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University , Kyoto 606-8501, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tsunematsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
mesh_terms: D001681:Biological Assay / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*; D013329:Structure-Activity Relationship; D016212:Transforming Growth Factor beta / Q000737:chemistry*
chemical_list: D009842:Oligopeptides; D016212:Transforming Growth Factor beta; C000600603:tryptopeptin A; C000600604:tryptopeptin B