[(2R,3S,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-2-(膦酰氧基甲基)四氢呋喃-3-基][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯 | 127067-28-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （3'->5'）-二核苷酸和类似物
• 中文名称: [(2R,3S,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-2-(膦酰氧基甲基)四氢呋喃-3-基][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯
• 英文名称: 5'-O-phosphoryl-2'-deoxycytidylyl-(3'->5')adenosine
• 英文别名: 2'-deoxy-cytidyl-(3',5')-adenosine；pdCpA；[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(phosphonooxymethyl)oxolan-3-yl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate
• CAS: 127067-28-1
• 化学式: C₁₉H₂₆N₈O₁₃P₂
• 分子量: 636.409
• InChiKey: UUBWXCHLJHRYJT-LNAOLWRRSA-N

物化性质

• 沸点：
  1024.7±75.0 °C(Predicted)
• 密度：
  2.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.8
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  310
• 氢给体数：
  7
• 氢受体数：
  17

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5’-三磷酸腺苷	ATP	56-65-5	C10H16N5O13P3	507.184
  ——	4-N-benzoyl-5'-O-[di(2-cyanoethyloxy)phosphoryl]-2'-deoxycytidylyl-{3'-OP-(2-cyanoethyl)->5'}-6-N,6-N,2'-O,3'-O-tetrabenzoyladenosine	127201-66-5	C63H55N11O18P2	1316.14
  5’-O-(4,4’-二甲氧基三苯基)-N4-苯甲酰基-2’-脱氧胞苷-3’-(2-氰乙基-N,N-二异丙基)亚磷酰胺	N4-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxycytidine-3-O-[O-(2-cyanoethyl)-N,N-(diisopropyl)]phosphoramidite	102212-98-6	C46H52N5O8P	833.921
  N4-苯甲酰基-5′-O-(4,4′-二甲氧基三苯基)-2′-脱氧胞苷	4-N-Benzoyl-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine	67219-55-0	C37H35N3O7	633.701

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	[(2R,3S,4R,5R)-2-[[[(2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-2-(phosphonooxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)-4-hydroxyoxolan-3-yl] (2S)-3-methyl-2-(pent-4-enoylamino)butanoate	187473-01-4	C29H41N9O15P2	817.643

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-2-(膦酰氧基甲基)四氢呋喃-3-基][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯 在 水 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 (S)-2-Hydroxy-propionic acid (2R,3R,4R,5R)-5-{[(2R,3S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-phosphonooxymethyl-tetrahydro-furan-3-yloxy]-hydroxy-phosphoryloxymethyl}-2-(6-amino-purin-9-yl)-4-hydroxy-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Incorporation of esters into proteins: Improved synthesis of hydroxyacyl tRNAs

  摘要：

  We describe two synthetic advances in the preparation of acylated suppressor transfer RNAs which significantly enhance the ease with which alpha-hydroxy acids can be incorporated into protein structures using nonsense suppression methods. We demonstrate that, in most cases, protection of the alpha-hydroxy group in the acylation reaction is not necessary. In cases where protection of the alpha-hydroxy group is desired, we further demonstrate the efficacy of the TBDMS protecting group over the more standard o-nitrobenzyl-based protecting groups. These advances greatly simplify the protocol for incorporation of alpha-hydroxy acids into proteins, overcome limitations associated with photoreactive sidechains, and suggest a general approach to improved suppression yields. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)01300-3
• 作为产物：
  描述：

  N4-苯甲酰基-5′-O-(4,4′-二甲氧基三苯基)-2′-脱氧胞苷 在 吡啶 、 四氮唑 、 ammonium hydroxide 、 四丁基氟化铵 、 水 、 碘 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 10.92h， 生成 [(2R,3S,5R)-5-(4-氨基-2-氧代嘧啶-1-基)-2-(膦酰氧基甲基)四氢呋喃-3-基][(2R,3S,4R,5R)-5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-基]甲基磷酸氢酯
  参考文献：
  名称：

  二核苷酸pdCpA和pdCpdA的改进的合成。

  摘要：

  为制备二核苷酸杂合体5'-O-磷酰基-2'-脱氧胞嘧啶-（3'-> 5'）腺苷（pdCpA）7开发了一条改进的途径。这种简单而简明的合成方法涉及2的连续偶联-氰基乙基N，N，N'，N'-四异丙基亚磷酰胺基与4-N-苯甲酰基-5'-O-（4，4'-二甲氧基三苯甲基）-2'-脱氧胞苷1和6-N，6- N，2'-O，3'-O-四苯甲酰腺苷2是关键步骤。还合成了一些带有不同保护基的二核苷酸衍生物，并详细研究了选择性脱保护条件。该方法在合成总DNA二核苷酸pdCpdA 17和总RNA二核苷酸21中的应用进一步证明了该方法的实用性和效率。

  DOI：

  10.1081/ncn-100002081

文献信息

• A general and efficient route for chemical aminoacylation of transfer RNAs
  作者：Stephanie A. Robertson、Jonathan A. Ellman、Peter G. Schultz

  DOI：10.1021/ja00007a055

  日期：1991.3

  The preparation of aminoacyl pdCpA in one step and in high yield by reaction of the cyanomethyl active esters of N-protected α-amino acids with pdCpA is detailed. The preparation and photodeprotection of aminoacyl pdCpA derivatives containing nitroveratryl (NVOC) N-protected amino acids is also studied. The utility of the above methods for preparing aminoacyl tRNA was confirmed by enzymatically ligating

  详述了通过N-保护的α-氨基酸的氰甲基活性酯与pdCpA反应一步高产率制备氨酰基pdCpA。还研究了含有硝基草酰 (NVOC) N 保护氨基酸的氨酰基 pdCpA 衍生物的制备和光脱保护。通过将 NVOC-苯丙氨酰 pdCpA 酶促连接到 tRNA-C OH，然后光解以提供未保护的苯丙氨酰 tRNA，证实了上述制备氨酰 tRNA 的方法的效用。苯丙氨酰 tRNA 被证明在体外蛋白质生物合成系统中是有能力的。这些协议极大地简化了化学错酰化 tRNA 在含有非天然氨基酸的蛋白质合成以及蛋白质生物合成研究中的使用
• Highly Sensitive Fluorescent Nonnatural Amino Acids That Can Be Incorporated into Specific Positions of Streptavidin
  作者：Masumi Taki、Takahiro Hohsaka、Hiroshi Murakami、Kazunari Taira、Masahiko Sisido

  DOI：10.1080/10426500213445

  日期：2002.8

  A small and highly fluorescent nonnatural amino acid that carries an anthraniloyl group was synthesized and incorporated into specific positions of streptavidin. The positions of the fluorescent amino acid were directed by CGGG/CCCG four-base codon /anticodon pair. The tRNA containing the four-base anticodon and charged with the fluorescent amino acid, was prepared as shown in Figure 1. In brief, the

  合成了一种带有邻氨基苯甲酰基的小且高度荧光的非天然氨基酸，并将其掺入链霉亲和素的特定位置。荧光氨基酸的位置由CGGG/CCCG四碱基密码子/反密码子对指示。含有四碱基反密码子并带有荧光氨基酸的 tRNA 制备如图 1 所示。简而言之，关键中间体（pdCpA 连接的氨基酸）3 被合成并与 tRNACCCG(-CA) 偶联T4 RNA 连接酶。然后，将氨酰化的 tRNA 4 与大肠杆菌 S30 裂解物的体外生物合成系统以及含有四碱基的突变链霉亲和素 mRNA 混合。
• Simultaneous and site-directed incorporation of an ester linkage and an azide group into a polypeptide by in vitro translation
  作者：Martin Humenik、Yiwei Huang、Igor Safronov、Mathias Sprinzl

  DOI：10.1039/b909188b

  日期：——

  A method is presented by which an azide-containing side chain can be introduced into any internal position of a polypeptide chain by in vitro translation. For this, 2′-deoxy-cytidylyl-(3′→5′)-adenosine was acylated on the 3′(2′)-hydroxyl group of adenosine with 6-azido-2(S)-hydroxyhexanoic acid (AHHA), an α-hydroxy- and ε-azide derivative of L-lysine. The acylated dinucleotide was enzymatically ligated with a tRNA transcript to provide chemically stable E. coli suppressor AHHA-tRNACys(CUA). The esterase 2 gene from Alicyclobacillus acidocaldarius was modified by the amber stop codon (UAG) on position 118. Using AHHA-tRNACys(CUA) in an E. coli in vitro translation/transcription system, the site-directed introduction of an azide group linked to a backbone ester into the esterase polypeptide was achieved. The yield of the synthesized modified protein reached 80% compared to translation of the native esterase. Subsequently, azide coupling with an alkyne-modified oligodeoxynucleotide demonstrated the feasibility of this approach for conjugation of polypeptides.

  本文介绍了一种方法，通过体外翻译技术，将含有叠氮的侧链引入多肽链的任意内部位置。为此，利用6-叠氮-2(S)-羟基己酸（AHHA）——L-赖氨酸的α-羟基和ε-叠氮衍生物，对2′-脱氧胞苷酰-(3′→5′)-腺苷酸的腺苷3′(2′)-羟基进行酰化。通过酶促连接反应，将酰化的二核苷酸与tRNA转录本结合，形成化学稳定的AHHA-tRNACys(CUA)大肠杆菌抑制子。对Alicyclobacillus acidocaldarius酯酶2基因的第118位进行修改，引入终止密码子UAG。在E. coli体外翻译/转录系统中使用AHHA-tRNACys(CUA)，实现了在酯酶多肽链中引入连接到骨架酯的叠氮基团。与天然酯酶的翻译相比，合成修饰蛋白的产量达到了80%。此后，叠氮与烷炔修饰的寡脱氧核苷酸的耦合实验证明了这种方法在多肽耦合中的可行性。
• Position-specific incorporation of a highly photodurable and blue-laser excitable fluorescent amino acid into proteins for fluorescence sensing
  作者：Hiroyuki Hamada、Naoko Kameshima、Aneta Szymańska、Katarzyna Wegner、Leszek Łankiewicz、Hiroaki Shinohara、Masumi Taki、Masahiko Sisido

  DOI：10.1016/j.bmc.2005.03.014

  日期：2005.5

  in the polarity of the environment. When the nonnatural amino acid was incorporated into specific positions of streptavidin, the mutant protein worked as a fluorescent sensor to biotin. Similarly, when the amino acid was incorporated into camel single-chain antibody, the mutant protein sensitively responded to the antigen molecule. The high incorporation efficiency, the high photodurability, the excitability

  使用4-碱基密码子/反密码子策略，将新的荧光氨基酸L-2- amino啶基丙氨酸掺入蛋白质的特定位置。掺入的效率足够高以获得足够数量的突变体。与经常用于生物学分析的常规荧光团相比，cri啶基在蓝色激光的波长下激发时具有很高的荧光性，并且具有很高的光耐久性。荧光强度对环境极性的微小变化敏感。当将非天然氨基酸掺入链霉亲和素的特定位置时，突变蛋白可作为生物素的荧光传感器。类似地，当将氨基酸掺入骆驼单链抗体中时，突变蛋白对抗原分子敏感地应答。
• Chemical aminoacylation of tRNAs with fluorinated amino acids for in vitro protein mutagenesis
  作者：Shijie Ye、Allison Ann Berger、Dominique Petzold、Oliver Reimann、Benjamin Matt、Beate Koksch

  DOI：10.3762/bjoc.6.40

  日期：——

  This article describes the chemical aminoacylation of the yeast phenylalanine suppressor tRNA with a series of amino acids bearing fluorinated side chains via the hybrid dinucleotide pdCpA and ligation to the corresponding truncated tRNA species. Aminoacyl-tRNAs can be used to synthesize biologically relevant proteins which contain fluorinated amino acids at specific sites by means of a cell-free translation system. Such engineered proteins are expected to contribute to our understanding of discrete fluorines’ interaction with canonical amino acids in a native protein environment and to enable the design of fluorinated proteins with arbitrary desired properties.

  本文描述了使用含有氟代侧链的一系列氨基酸通过杂交二核苷酸pdCpA化学氨酰化酵母苯丙氨酸抑制子tRNA，并与相应的截短tRNA物种连接。氨酰-tRNA可以用于通过无细胞翻译系统在特定位点合成含有氟代氨基酸的生物学相关蛋白质。这种工程蛋白质有望为我们了解离散氟元素在天然蛋白质环境中与基本氨基酸的相互作用以及设计具有任意所需特性的氟化蛋白质做出贡献。