N-(4-pentenoyl)-(S)-alanine cyanomethyl ester | 201869-55-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(4-pentenoyl)-(S)-alanine cyanomethyl ester
• 英文别名: N-(4-pentenoyl)-L-alanine cyanomethyl ester；N-(4-pentenoyl)-S-alanine cyanomethyl ester；N-pent-4-enoyl-L-alanine cyano-methyl ester；cyanomethyl (2S)-2-(pent-4-enoylamino)propanoate
• CAS: 201869-55-8
• 化学式: C₁₀H₁₄N₂O₃
• 分子量: 210.233
• InChiKey: WVUWLXSPXZGTRD-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-pentenoyl)-(S)-alanine cyanomethyl ester 、 UMP bis(tetra-n-butylammonium salt) 在 水 、 碘 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.83h， 生成 bis-2',3'-O-alanyl-UMP
  参考文献：
  名称：

  Structural Basis for the Exceptional Stability of Bisaminoacylated Nucleotides and Transfer RNAs

  摘要：

  At least one bisaminoacyl-tRNA is synthesized in nature (by Therm us thermophilus phenylalanyl-tRNA synthetase), and many disubstituted tRNAs have been prepared in vitro. Such misacylated tRNAs are able to participate in protein synthesis, even though they lack the free 2'-OH group of the 3'-terminal adenosine moiety. Their ready participation in protein synthesis implies significant chemical reactivity. The basis for this reactivity has been documented previously. Surprisingly, the aminoacyl moieties of these tRNAs also exhibit exceptional chemical stability. In the present report, bisaminoacylated nucleotides are investigated computationally and experimentally to define the basis for the stability of such species. Molecular modeling of bisalanyl-AMP in the absence of solvent and in the presence of a limited number of water molecules revealed two common features among the low-energy structures. The first was the presence of H-bonding interactions between the two aminoacyl moieties. The second was the presence of a H-bonding interaction between the 2'-O-alanyl moiety and the N-3 atom of the adenine nucleobase, typically mediated through a water molecule. The prediction of an interaction between an aminoacyl moiety and the adenine nudeobase was confirmed experimentally by comparing the behavior of bisalanyl-AMP and bisalanyl-UMP in the presence of model nucleophiles. This study suggests a possible role for the adenosine moiety at the 3'-end of aminoanyl-tRNAs in controlling the stability and reactivity of the aminoacyl moiety and has important implications for the reactivity and stability of normal aminoacyl-tRNAs.

  DOI：

  10.1021/ja203994e
• 作为产物：
  描述：

  4-戊烯酸 在 N-甲基吗啉 、 lithium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 41.0h， 生成 N-(4-pentenoyl)-(S)-alanine cyanomethyl ester
  参考文献：
  名称：

  具有化学可移动保护基的错误酰化的转移RNA。

  摘要：

  已经研究了4-戊烯酰基和许多衍生物作为错误酰基化的tRNA中氨基酰基部分的Nα的保护基。发现未取代的4-戊烯酰基本身与任何研究的衍生物一样有效地起作用。制备了四种不同的N-（4-戊烯酰基）氨基酰基-tRNA（CUA），并显示在与碘水溶液混合后易于进行脱保护。在体外蛋白质生物合成系统中，衍生的错误酰化的tRNA都可作为无义密码子的抑制剂发挥良好的功能。还制备了在侧链羧酸酯上被保护的四个Nα-（4-戊烯酰基）天冬氨酰-tRNA（CUA），作为硝化过的烷基酯。用碘水溶液处理后 通过抑制mRNA中的UAG密码子，错误酰化的抑制性tRNA将天冬氨酸衍生物掺入二氢叶酸还原酶的27位。抑制产量明显好于没有侧链保护时的抑制产量。所得的“笼状蛋白”是无活性的，但是在足以使侧链羧酸酯部分脱保护的条件下，通过辐照恢复了全部催化潜力。

  DOI：

  10.1021/jo971692l

文献信息

• Decoding the Logic of the tRNA Regiospecificity of Nonribosomal FemXWv Aminoacyl Transferase
  作者：Matthieu Fonvielle、Maryline Chemama、Maxime Lecerf、Régis Villet、Patricia Busca、Ahmed Bouhss、Mélanie Ethève-Quelquejeu、Michel Arthur

  DOI：10.1002/anie.201001473

  日期：——

  Natural selection: Replacement of the 3′‐OH group of Ala‐tRNAAla with 3′‐H affected FemXWv‐catalyzed aminoacyl transfer from the 2′‐position, but not substrate binding. The ability of FemXWv to bind and transacylate the 3′‐O‐Ala isomer initially formed by alanyl‐tRNA synthetase (AlaRS) may be crucial for efficient competition with the ribosome (see scheme).

  自然选择：用3'-H影响的FemX Wv催化的氨基酰基从2'-位转移来取代Ala-tRNA Ala的3'-OH基团，但不影响底物结合。FemX Wv结合并通过丙氨酰tRNA合成酶（AlaRS）最初形成的3'-O-Ala异构体的能力可能对与核糖体的有效竞争至关重要（请参阅方案）。
• Synthesis of 3′-Fluoro-tRNA Analogues for Exploring Non-ribosomal Peptide Synthesis in Bacteria
  作者：Laura Iannazzo、Guillaume Laisné、Matthieu Fonvielle、Emmanuelle Braud、Jean-Philippe Herbeuval、Michel Arthur、Mélanie Etheve-Quelquejeu

  DOI：10.1002/cbic.201402523

  日期：2015.2.9

  Fluorinated aminoacyl‐tRNA analogues: Semisynthetic routes to fluoro analogues of tRNAAla and Ala‐tRNAAla have been developed. These molecules are non‐isomerisable analogues of the substrates of alanyl‐tRNA synthetases and FemX transferases and should provide new insight into substrate recognition by these enzymes.

  氟化氨-酰tRNA类似物：半合成路线的tRNA的氟类似物丙氨酸和Ala-tRNA的丙氨酸已经开发出来。这些分子是丙氨酰-tRNA合成酶和FemX转移酶底物的不可异构类似物，应该为这些酶对底物的识别提供新的见解。
• Modeling the reactive properties of tandemly activated tRNAs
  作者：Maria Duca、Shengxi Chen、Sidney M. Hecht

  DOI：10.1039/b806790b

  日期：——

  Tandemly activated tRNAs, bearing amino acid moieties at both the 2′- and 3′-positions of the 3′-terminal adenosine moiety (A76), have been shown to participate efficiently in protein synthesis [B. Wang, J. Zhou, M. Lodder, R. D. Anderson, III and S. M. Hecht, J. Biol. Chem., 2006, 281, 13865]. The mechanism by which such activated tRNAs are able to donate both amino acids to the growing polypeptide chain is not well understood. Here we report the chemical behavior and participation in protein synthesis of new bisaminoacyl derivatives of pdCpA and tRNA. Both amino moieties of the aminoacyl groups are shown to be important to enable participation in protein synthesis; paradoxically, they also confer an unanticipated chemical stability toward different nucleophiles. The results obtained suggest a model for participation of bisaminoacylated tRNAs in protein synthesis.

  Wang, J. Zhou, M. Lodder, R. D. Anderson, III and S. M. Hecht, J. Biol.Chem.，2006，281，13865]。这种活化的 tRNA 能够向生长中的多肽链提供两种氨基酸的机制尚不十分清楚。在这里，我们报告了 pdCpA 和 tRNA 的新双氨基酰衍生物的化学行为和参与蛋白质合成的情况。结果表明，氨基酰基的两个氨基对参与蛋白质合成非常重要；矛盾的是，它们还赋予了对不同亲核物的化学稳定性，这一点出乎意料。研究结果表明了双氨基酰化 tRNA 参与蛋白质合成的模式。
• Positional assignment of differentially substituted bisaminoacylated pdCpAs
  作者：David J. Maloney、Noha Ghanem、Jia Zhou、Sidney M. Hecht

  DOI：10.1039/b708786a

  日期：——

  The synthesis and NMR analysis of a 2′-O-alanyl, 3′-O-[1-13C]valyl-pdCpA derivative has permitted the definitive assignment of the positions of acylation of tandemly activated pdCpAs, and the bisaminoacylated transfer RNAs derived therefrom.

  通过合成和核磁共振分析 2′-O-丙氨酰、3′-O-[1-13C]缬氨酰-pdCpA 衍生物，可以确定串联活化 pdCpAs 的酰化位置，以及由此衍生的双氨基酰化转移 RNA。
• Synthesis of bisaminoacylated pdCpAs and tandemly activated transfer RNAs
  作者：Maria Duca、David J. Maloney、Michiel Lodder、Bixun Wang、Sidney M. Hecht

  DOI：10.1016/j.bmc.2007.03.088

  日期：2007.7

  Described herein is the preparation of new bisacylated tRNAs and their participation in protein synthesis. It has been reported that Thermus thermophilus phenylalanyl-tRNA synthetase can introduce two phenylalanine moieties onto the 3'-terminal adenosine of its cognate tRNA. It is also possible to prepare bisactivated tRNAs in vitro; these participate in protein synthesis [Wang, B.; Zhou, J.; Lodder, M.; Anderson, R. D.; Hecht, S. M. J Biol. Chem. 2006, 281, 138651. Presently, the chemical strategy used for the synthesis of the key intermediate bisacylated pdCpAs is described. Bis-S-alanyl- and bis-S-methionyl-pdCpAs were prepared initially. Further, S-threonine, S-allo-threonine, S-homoserine, and (S)-(+)-2-amino-3-hydroxy-3-methylbutyric acid were coupled with the dinucleotide to define preparative methods applicable to more complex amino acids bearing additional functionality in the form of an OH group. (c) 2007 Elsevier Ltd. All rights reserved.