[(2R,3S,4R,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲基[羟基-[(2R,3S,4S)-2,3,4,5-四羟基戊氧基]磷酰]磷酸氢酯 | 3506-17-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 中文名称: [(2R,3S,4R,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲基[羟基-[(2R,3S,4S)-2,3,4,5-四羟基戊氧基]磷酰]磷酸氢酯
• 英文名称: cytidine diphosphate ribitol
• 英文别名: CDP-ribitol；diphosphoric acid-1-cytidin-5'-yl ester-2-L-ribitol-1-yl ester；Diphosphorsaeure-1-cytidin-5'-ylester-2-L-ribit-1-ylester；[[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4S)-2,3,4,5-tetrahydroxypentyl] hydrogen phosphate
• CAS: 3506-17-0
• 化学式: C₁₄H₂₅N₃O₁₅P₂
• 分子量: 537.311
• InChiKey: DPJKHFICSGCNIR-HRENORGGSA-N

物化性质

• 沸点：
  916.0±75.0 °C(Predicted)
• 密度：
  2.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -6.5
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  292
• 氢给体数：
  9
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  O-[2-N-(4-nitro)benzamidoethyl 2-acetamido-2-deoxy-β-D-galactopyranoside] 3-(D-ribit-5-yltriethylammonium phosphate) 、 [(2R,3S,4R,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲基[羟基-[(2R,3S,4S)-2,3,4,5-四羟基戊氧基]磷酰]磷酸氢酯 在 Fukutin-related protein 作用下， 以 aq. buffer 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  含磷酸核糖醇的多糖的化学和化学酶促合成 Matriglycan 支架

  摘要：

  核糖醇磷酸对核心 M3 O -甘露糖基聚糖的修饰对于α-肌营养不良聚糖的功能成熟很重要。包括串联磷酸核糖醇在内的核心 M3 O -甘露糖基聚糖的三个连续延伸的部分结构被区域选择性和立体选择性合成：Rbo5P-3GalNAcβ、Rbo5P-1Rbo5P-3GalNAcβ 和 Xylβ1-4Rbo5P-1Rbo5P-3GalNAcβ（Rbo5P，d -核糖醇-5-磷酸；GalNAc，N-乙酰基-d-半乳糖胺；Xyl，d-木糖）。Rbo5P-3GalNAcβ 与p苷元部分的-硝基苯基作为核糖醇磷酸转移酶（FKRP，福库丁相关蛋白）的底物，其产物在一系列糖基转移酶的作用下被糖基化，即核糖醇木糖基转移酶1（RXYLT1）、β1,4-葡萄糖醛酸转移酶 1 (B4GAT1) 和类似乙酰氨基葡萄糖转移酶 (LARGE)。配备炔烃型糖苷配基的 Rbo5P-3GalNAcβ 对 FKRP 也有活性。在 FKRP

  DOI：

  10.1021/acschembio.2c00181
• 作为产物：
  描述：

  5'-胞苷酸 在 吡啶 、 sodium tetrahydroborate 、 三正丁胺 、 水 、 N,N'-二环己基碳二亚胺 作用下， 生成 [(2R,3S,4R,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-3,4-二羟基四氢呋喃-2-基]甲基[羟基-[(2R,3S,4S)-2,3,4,5-四羟基戊氧基]磷酰]磷酸氢酯
  参考文献：
  名称：

  Baddiley et al., Journal of the Chemical Society, 1959, p. 2192,2194

  摘要：

  DOI：

文献信息

• Therapeutic agent for diseases associated with abnormalities in dystroglycan sugar chain modification and method for assaying associated enzyme
  申请人：NATIONAL UNIVERSITY CORPORATION KOBE UNIVERSITY

  公开号：US11040087B2

  公开（公告）日：2021-06-22

  Provided is a therapeutic agent that effectively acts on a disease associated with abnormal glycosylation of dystroglycan. Also provided is a testing method for diseases associated with abnormal glycosylation of dystroglycan. Specifically, provided is a therapeutic agent for diseases associated with abnormal glycosylation of dystroglycan, containing CDP-ribitol as an active ingredient. Ribitol-phosphate is important in the glycan structure of dystroglycan. In order for ribitol-phosphate to be incorporated into a dystroglycan glycan, a material therefor (sugar donor) is required. In the present invention, it has been found for the first time that CDP-ribitol serves as the sugar donor. It has been confirmed that the glycan of ISPD-deficient cells can be restored by administering CDP-ribitol. Thus, the present invention, which allows CDP-ribitol to be utilized for supplementation therapy, has been completed.

  本发明提供了一种治疗剂，可有效治疗与肌张力蛋白糖基化异常相关的疾病。还提供了一种与肌张力蛋白糖基化异常相关疾病的检测方法。具体而言，本发明提供了一种治疗与肌张力蛋白糖基化异常相关疾病的药物，其有效成分为 CDP-核糖醇。核糖醇-磷酸在肌张力蛋白的聚糖结构中非常重要。为了将核糖醇-磷酸结合到肌张力蛋白聚糖中，需要一种材料（糖供体）。在本发明中，首次发现 CDP 核糖醇可作为糖供体。经证实，通过施用 CDP-ribitol 可以恢复 ISPD 缺陷细胞的聚糖。因此，本发明已经完成，可以利用 CDP-ribitol 进行补充治疗。
• Staphylococcus aureus and Bacillus subtilis W23 Make Polyribitol Wall Teichoic Acids Using Different Enzymatic Pathways
  作者：Stephanie Brown、Timothy Meredith、Jonathan Swoboda、Suzanne Walker

  DOI：10.1016/j.chembiol.2010.07.017

  日期：2010.10

  Wall teichoic acids (WTAs) are anionic polymers that play key roles in bacterial cell shape, cell division, envelope integrity, biofilm formation, and pathogenesis B subtilis W23 and S aureus both make polyribitol-phosphate (RboP) WTAs and contain similar sets of biosynthetic genes We use in vitro reconstitution combined with genetics to show that the pathways for WTA biosynthesis in B subtilis W23 and S aureus are different S aureus requires a glycerol-phosphate primase called TarF in order to make RboP-WTAs, B subtilis W23 contains a TarF homolog, but this enzyme makes glycerol-phosphate polymers and is not involved in RboP-WTA synthesis Instead, B subtilis TarK functions in place of TarF to prime the WTA intermediate for chain extension by TarL This work highlight:, the enzymatic diversity of the poorly characterized family of phosphotransferases involved in WTA biosynthesis in Gram-positive organisms
• Therapeutic Agent For Diseases Associated With Abnormalities In Dystroglycan Sugar Chain Modification And Method For Assaying Associated Enzyme
  申请人：NATIONAL UNIVERSITY CORPORATION KOBE UNIVERSITY

  公开号：US20200188491A1

  公开（公告）日：2020-06-18

  Provided is a therapeutic agent that effectively acts on a disease associated with abnormal glycosylation of dystroglycan. Also provided is a testing method for diseases associated with abnormal glycosylation of dystroglycan. Specifically, provided is a therapeutic agent for diseases associated with abnormal glycosylation of dystroglycan, containing CDP-ribitol as an active ingredient. Ribitol-phosphate is important in the glycan structure of dystroglycan. In order for ribitol-phosphate to be incorporated into a dystroglycan glycan, a material therefor (sugar donor) is required. In the present invention, it has been found for the first time that CDP-ribitol serves as the sugar donor. It has been confirmed that the glycan of ISPD-deficient cells can be restored by administering CDP-ribitol. Thus, the present invention, which allows CDP-ribitol to be utilized for supplementation therapy, has been completed.
• Baddiley et al., Journal of the Chemical Society, 1959, p. 2192,2194
  作者：Baddiley et al.

  DOI：——

  日期：——
• Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan
  作者：Jun-ichi Tamura、Takahiro Tamura、Shunsuke Hoshino、Rieko Imae、Ryuichi Kato、Mizuki Yokono、Mao Nagase、Shiho Ohno、Noriyoshi Manabe、Yoshiki Yamaguchi、Hiroshi Manya、Tamao Endo

  DOI：10.1021/acschembio.2c00181

  日期：2022.6.17

  N-acetyl-d-galactosamine; Xyl, d-xylose). Rbo5P-3GalNAcβ with p-nitrophenyl at the aglycon part served as a substrate for ribitol phosphate transferase (FKRP, fukutin-related protein), and its product was glycosylated by the actions of a series of glycosyltransferases, namely, ribitol xylosyltransferase 1 (RXYLT1), β1,4-glucuronyltransferase 1 (B4GAT1), and like-acetyl-glucosaminyltransferase (LARGE).

  核糖醇磷酸对核心 M3 O -甘露糖基聚糖的修饰对于α-肌营养不良聚糖的功能成熟很重要。包括串联磷酸核糖醇在内的核心 M3 O -甘露糖基聚糖的三个连续延伸的部分结构被区域选择性和立体选择性合成：Rbo5P-3GalNAcβ、Rbo5P-1Rbo5P-3GalNAcβ 和 Xylβ1-4Rbo5P-1Rbo5P-3GalNAcβ（Rbo5P，d -核糖醇-5-磷酸；GalNAc，N-乙酰基-d-半乳糖胺；Xyl，d-木糖）。Rbo5P-3GalNAcβ 与p苷元部分的-硝基苯基作为核糖醇磷酸转移酶（FKRP，福库丁相关蛋白）的底物，其产物在一系列糖基转移酶的作用下被糖基化，即核糖醇木糖基转移酶1（RXYLT1）、β1,4-葡萄糖醛酸转移酶 1 (B4GAT1) 和类似乙酰氨基葡萄糖转移酶 (LARGE)。配备炔烃型糖苷配基的 Rbo5P-3GalNAcβ 对 FKRP 也有活性。在 FKRP