6-cyanouridine 5'-monophosphate | 68244-52-0

• 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
• 英文名称: 6-cyanouridine 5'-monophosphate
• 英文别名: ((2R,3S,4R,5R)-5-(6-cyano-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate；6-Cyanouridine 5'-Phosphate；[(2R,3S,4R,5R)-5-(6-cyano-2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
• CAS: 68244-52-0
• 化学式: C₁₀H₁₂N₃O₉P
• 分子量: 349.194
• InChiKey: GCVKNFUDFHDSJQ-ZOQUXTDFSA-N

物化性质

• 密度：
  1.91±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  190
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-cyanouridine 5'-monophosphate 在 钯 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、6.08 MPa 条件下， 反应 2.0h， 生成 6-methylaminouridine 5'-phosphate
  参考文献：
  名称：

  OMP Decarboxylase:  An Experimental Test of Electrostatic Destabilization of the Enzyme−Substrate Complex

  摘要：

  6-Methylaminouridine 5'-phosphate (MAUMP) inhibits OMP decarboxylase (Ki = 3 x 10-6 M) maximally at pH values where its amino group is uncharged. Comparison of the chemical shift of free [7-13C]-MAUMP in solutions of varying pH, with that of the enzyme-bound species confirms that this inhibitor is bound with its amino group uncharged. This enzyme's apparent lack of affinity for a cationic substituent, located near the position that would ordinarily be occupied by the scissile carboxylate group of the substrate, does not appear to support the view that the E-S complex is destabilized by electrostatic repulsion in the ground state.

  DOI：

  10.1021/ja0450049
• 作为产物：
  描述：

  在 水 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 6-cyanouridine 5'-monophosphate
  参考文献：
  名称：

  WO2007/38859

  摘要：

  公开号：

文献信息

• OLIGONUCLEOTIDE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20150376611A1

  公开（公告）日：2015-12-31

  The present invention provides an oligonucleotide having improved affinity for AGO2, and the like. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like) or formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like} at the 5′ end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3.

  本发明提供了一种具有改善对AGO2亲和力的寡核苷酸等。该寡核苷酸在其5'端具有由式(I)表示的核苷酸残基或核苷酸残基其中X 1 是氧原子或类似物，R 1 是式(IIA)（其中R 5A 是卤素或类似物，而R 6A 是氢原子或类似物）或式(IVA)（其中Y 3A 是氮原子或类似物，而Y 4A 是CH或类似物），或类似物，R 2 是氢原子、羟基、卤素或可选择地取代的较低烷氧基，而R 3 是氢原子或类似物}，并且该核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• OLIGONUCLEOTIDE HAVING NON-NATURAL NUCLEOTIDE AT 5'-TERMINAL THEREOF
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：US20170354673A1

  公开（公告）日：2017-12-14

  An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) wherein X 1 is an oxygen atom or the like, R 1 is formula (IIA) (wherein R 5A is halogen or the like, and R 6A is a hydrogen atom or the like), formula (IVA) (wherein Y 3A is a nitrogen atom or the like, and Y 4A is CH or the like), or the like, R 2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R 3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

  具有由式(I)表示的核苷酸残基或核苷酸残基的寡核苷酸其中X1是氧原子或类似物，R1是式(IIA)（其中R5A是卤素或类似物，而R6A是氢原子或类似物），式(IVA)（其中Y3A是氮原子或类似物，而Y4A是CH或类似物），或类似物，R2是氢原子，羟基，卤素，或可选择地取代的较低烷氧基，而R3是氢原子或类似物，或式(VI)（其中n2为1、2或3）}在其5'端，其中核苷酸残基或核苷酸残基通过位于位置3的氧原子与相邻核苷酸残基结合。
• An Unprecedented Twist to ODCase Catalytic Activity
  作者：Masahiro Fujihashi、Angelica M. Bello、Ewa Poduch、Lianhu Wei、Subhash C. Annedi、Emil F. Pai、Lakshmi P. Kotra

  DOI：10.1021/ja054865u

  日期：2005.11.1

  Orotidine-5'-monophosphate decarboxylase (ODCase) has evolved to catalyze a decarboxylation reaction, most probably via a carbanion species at the C6 position of orotidine-5'-monophosphate. We reveal an unusual biochemical pathway of conversion of 6-cyano-uridine-5'-monophosphate by ODCase to barbiturate-5'-monophosphate via perhaps an electrophilic center at the C6 position, leading to inhibition

  Orotidine-5'-monophosphate decarboxylase (ODCase) 已经进化为催化脱羧反应，最有可能是通过 orotidine-5'-monophosphate 的 C6 位置的碳负离子物种。我们揭示了 ODCase 将 6-cyano-uridine-5'-monophosphate 转化为 barbiturate-5'-monophosphate 的一种不寻常的生化途径，可能通过 C6 位置的亲电子中心，导致抑制。ODCase 的这种潜力在设计新型抑制剂时非常有用。
• Lys314 is a Nucleophile in Non-Classical Reactions of Orotidine-5′-Monophosphate Decarboxylase
  作者：Daniel Heinrich、Ulf Diederichsen、Markus Georg Rudolph

  DOI：10.1002/chem.200900397

  日期：2009.7.6

  Molecular versatility: Unusual reactivities such as hydrolysis, nucleophilic aromatic substitution, and addition reactions of human orotidine‐5′‐monophosphate decarboxylase are explained by crystal structures and involve a nucleophilic lysine residue that normally is expected to act solely as a general base (RP=phosphoribosyl, R=CO2H, CN, acetyl, N3, I; R′=OH, SH, acetyl, hydroxymethyl).

  分子多功能性：异常的反应性，例如水解，亲核芳香族取代以及人orotidine-5'-单磷酸脱羧酶的加成反应，都由晶体结构解释，并且涉及亲核赖氨酸残基，通常预期其仅作为一般碱基起作用（RP =磷酸核糖基，R ＝ CO 2 H，CN，乙酰基，N 3，I； R′＝ OH，SH，乙酰基，羟甲基）。
• A substantial oxygen isotope effect at O2 in the OMP decarboxylase reaction: Mechanistic implications
  作者：Wickliffe O. Wepukhulu、Vanessa L. Smiley、Bhargavi Vemulapalli、Jeffrey A. Smiley、Linda M. Phillips、Jeehiun K. Lee

  DOI：10.1039/b812979g

  日期：——

  Orotidine-5'-monophosphate decarboxylase (OMP decarboxylase, ODCase) catalyzes the decarboxylation of orotidine-5'-monophosphate (OMP) to uridine-5'-monophosphate (UMP). Despite extensive enzymological, structural, and computational studies, the mechanism of ODCase remains incompletely characterized. Herein, carbon kinetic isotope effects were measured for both the natural abundance substrate and a

  Orotidine-5'-单磷酸脱羧酶（OMP脱羧酶，ODCase）催化orotidine-5'-单磷酸（OMP）脱羧为尿苷5'-单磷酸（UMP）。尽管进行了广泛的酶学，结构和计算研究，但ODCase的机制仍未完全表征。在此，对于自然丰度底物和为了进行远程双标记同位素效应程序而合成的底物混合物，均以底物的O 2为远程位置，测量了碳动力学同位素效应。测得该底物混合物对酶促脱羧的碳动力学同位素效应为1.0199 +/- 0.0007，而自然丰度OMP的值为1.0289 +/- 0.0009，表明（18）O2同位素效应为0.991 +/- 0.001。使用从先前同位素效应数据得出的计算承诺因子，该值等于约0.983的固有同位素效应。测得的（18）O2同位素效应需要一种或多种酶促过程的机制，包括结合和/或化学作用，从而促成这种实质性的反同位素效应。（18）针对两种拟议的机理计算了O2的动力学同位素