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更新于：2025-05-07

Chloroorienticin B

更新于：2025-05-07

概要

概要

基本信息

药物类型

化学药

别名

靶点-

作用方式-

作用机制-

治疗领域

感染

在研适应症-

非在研适应症

革兰氏阳性细菌感染

原研机构

Shionogi & Co., Ltd.

在研机构-

非在研机构

Shionogi & Co., Ltd.

权益机构-

最高研发阶段终止临床阶段不明

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构/序列

分子式C66H75Cl2N9O24

InChIKeyATHQCOUEZPBNLP-JWYJDYCQSA-N

CAS号118373-81-2

关联

100 项与 Chloroorienticin B 相关的临床结果

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100 项与 Chloroorienticin B 相关的转化医学

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100 项与 Chloroorienticin B 相关的专利（医药）

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项与 Chloroorienticin B 相关的文献（医药）

2005-08-01·Journal of the American Chemical Society1区 · 化学

A Systematic Investigation of the Synthetic Utility of Glycopeptide Glycosyltransferases

1区 · 化学

Article

作者: Walsh, Christopher T. ; Kruger, Ryan G. ; Leimkuhler, Catherine ; Oberthür, Markus ; Kahne, Daniel ; Lu, Wei

Glycosyltransferases involved in the biosynthesis of bacterial secondary metabolites may be useful for the generation of sugar-modified analogues of bioactive natural products. Some glycosyltransferases have relaxed substrate specificity, and it has been assumed that promiscuity is a feature of the class. As part of a program to explore the synthetic utility of these enzymes, we have analyzed the substrate selectivity of glycosyltransferases that attach similar 2-deoxy-L-sugars to glycopeptide aglycons of the vancomycin-type, using purified enzymes and chemically synthesized TDP beta-2-deoxy-L-sugar analogues. We show that while some of these glycopeptide glycosyltransferases are promiscuous, others tolerate only minor modifications in the substrates they will handle. For example, the glycosyltransferases GtfC and GtfD, which transfer 4-epi-L-vancosamine and L-vancosamine to C-2 of the glucose unit of vancomycin pseudoaglycon and chloroorienticin B, respectively, show moderately relaxed donor substrate specificities for the glycosylation of their natural aglycons. In contrast, GtfA, a transferase attaching 4-epi-L-vancosamine to a benzylic position, only utilizes donors that are closely related to its natural TDP sugar substrate. Our data also show that the spectrum of donors utilized by a given enzyme can depend on whether the natural acceptor or an analogue is used, and that GtfD is the most versatile enzyme for the synthesis of vancomycin analogues.

2004-03-30·Proceedings of the National Academy of Sciences1区 · 综合性期刊

Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin

1区 · 综合性期刊

Article

作者: Walsh, Christopher T. ; Oberthür, Markus ; Tao, Junhua ; Kahne, Daniel ; Lu, Wei ; Leimkuhler, Catherine

Chloroeremomycin, a vancomycin family glycopeptide antibiotic has three sugars, one d -glucose and two l -4- epi -vancosamines, attached to the crosslinked heptapeptide backbone by three glycosyltransferases, GtfA, -B, and -C. Prior efforts have revealed that GtfB and -C in tandem build an epivancosaminyl-1,2-glucosyldisaccharide chain on residue 4 of the aglycone; however, the characterization of GtfA and glycosylation sequence of chloroeremomycin have been lacking. Here, we report the expression and purification of GtfA, as well as synthesis of its sugar donor, 2′-deoxy-thymidine 5′-diphosphate (dTDP)-β- l -4- epi -vancosamine. GtfA transfers 4- epi -vancosamine from the chemically synthesized dTDP-4- epi -vancosamine to the β-OH-Tyr 6 residue of the aglycone, preferentially after GtfB action, to generate chloroorienticin B. With the preferred kinetic order of GtfB, then GtfA, then GtfC established, we have succeeded in reconstitution of chloroeremomycin from the heptapeptide aglycone by the sequential actions of the three enzymes.

2002-11-01·Bioorganic & Medicinal Chemistry Letters4区 · 医学

Novel semi-synthetic glycopeptide antibiotics active against methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE): doubly-modified water-soluble derivatives of chloroorienticin B

4区 · 医学

Article

作者: Yasuhiro Nishitani ; Tadashi Munekage ; Tatsuro Yasukata ; Yukitoshi Narukawa ; Yukihito Sumino ; Osamu Yoshida

A series of N-alkylated and aminomethylated derivatives of chloroorienticin B, a vancomycin-related glycopeptide antibiotic, were synthesized. Doubly-modified derivatives having both hydrophobic and hydrophilic substituents exhibited potent antibacterial activity against MRSA and VRE along with considerable water-solubility.

100 项与 Chloroorienticin B 相关的药物交易

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研发状态

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2014	N/A	非小细胞肺癌	-	Cucurbitacin B	築製膚鹽廠觸艱築衊醖(遞餘醖鹽選鹹製窪窪鹽) = 鹹簾簾蓋壓醖選顧壓繭繭製淵齋壓壓憲觸顧醖 (繭窪網憲顧壓艱鹹網窪 )	积极	2014-10-01
				Cucurbitacin B (Control (normal human bronchial epithelial cells))	簾遞製網顧範蓋願鹽築(餘鑰鹹憲鑰廠餘範蓋餘) = 獵醖艱餘繭觸蓋積蓋築願獵衊窪壓範獵範窪獵 (衊製衊製蓋繭選餘夢衊 )
AACR2010	N/A	乳腺癌	-	Cucurbitacin B	築鏇糧夢鑰壓積鑰壓壓(觸餘廠廠遞顧繭壓鹽廠) = 憲壓積夢選鹹積顧網憲艱製醖鬱廠構鹹艱膚窪 (願淵壓積衊願醖窪鏇膚 )	-	2010-04-15
				Dihydrocucurbitacin B	築鏇糧夢鑰壓積鑰壓壓(觸餘廠廠遞顧繭壓鹽廠) = 憲鬱鏇鹽範選艱簾選醖艱製醖鬱廠構鹹艱膚窪 (願淵壓積衊願醖窪鏇膚 )