2724-56-3Relevant articles and documents
Carrier Protein-Free Enzymatic Biaryl Coupling in Arylomycin A2 Assembly and Structure of the Cytochrome P450 AryC**
Aldemir, Hülya,Einsiedler, Manuel,Gulder, Tobias A. M.,Harteis, Sabrina,Hong, Hanna,Milzarek, Tobias M.,Richarz, René,Schaefers, Francoise,Schneider, Sabine,Shu, Shuangjie
, (2021/11/30)
The arylomycin antibiotics are potent inhibitors of bacterial type I signal peptidase. These lipohexapeptides contain a biaryl structural motif reminiscent of glycopeptide antibiotics. We herein describe the functional and structural evaluation of AryC, the cytochrome P450 performing biaryl coupling in biosynthetic arylomycin assembly. Unlike its enzymatic counterparts in glycopeptide biosynthesis, AryC converts free substrates without the requirement of any protein interaction partner, likely enabled by a strongly hydrophobic cavity at the surface of AryC pointing to the substrate tunnel. This activity enables chemo-enzymatic assembly of arylomycin A2 that combines the advantages of liquid- and solid-phase peptide synthesis with late-stage enzymatic cross-coupling. The reactivity of AryC is unprecedented in cytochrome P450-mediated biaryl construction in non-ribosomal peptides, in which peptidyl carrier protein (PCP)-tethering so far was shown crucial both in vivo and in vitro.
New hydroxamic acid derivative and use thereof
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, (2016/12/07)
PROBLEM TO BE SOLVED: To provide a novel hydroxamic acid derivative having an inhibitory activity against KDM7 being a histone demethylase, and a cancer cell proliferation-suppressing action, and to provide medicines (particularly a KDM7 inhibitor and anticancer agent) using the derivative.SOLUTION: A compound represented by general formula (I) (wherein R is a linear, branched or annular alkyl group; and n is an integer of ≥6), a salt thereof, hydrate, solvate or prodrug are provided. The compound can be used as a medicine (particularly an anticancer agent) or a KDM7 inhibitor.
Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity
Suzuki, Takayoshi,Ozasa, Hiroki,Itoh, Yukihiro,Zhan, Peng,Sawada, Hideyuki,Mino, Koshiki,Walport, Louise,Ohkubo, Rei,Kawamura, Akane,Yonezawa, Masato,Tsukada, Yuichi,Tumber, Anthony,Nakagawa, Hidehiko,Hasegawa, Makoto,Sasaki, Ryuzo,Mizukami, Tamio,Schofield, Christopher J.,Miyata, Naoki
, p. 7222 - 7231 (2013/10/21)
Histone Nε-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.