(E)-4-(4-nitrophenoxy)-4-oxobut-2-enoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: (E)-4-(4-nitrophenoxy)-4-oxobut-2-enoic acid
• 英文别名: mono(p-nitrophenyl) fumarate；mono p-nitrophenyl fumarate；mono-p-nitrophenyl fumarate
• 化学式: C₁₀H₇NO₆
• 分子量: 237.169
• InChiKey: CEZOWBQTNAYMRA-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-4-(4-nitrophenoxy)-4-oxobut-2-enoic acid 在 KO-42 polypeptide 作用下， 以 水 为溶剂， 生成 对硝基苯酚
  参考文献：
  名称：

  Catalysis of Hydrolysis and Transesterification Reactions of p-Nitrophenyl Esters by a Designed Helix−Loop−Helix Dimer

  摘要：

  KO-42, a polypeptide with 42 amino acid residues has been designed to fold into a hairpin helix-loop-helix motif that dimerizes and forms a four-helix bundle. The solution structure of the folded KO-42 dimer has been determined by NMR and CD spectroscopy and ultracentrifugation. On the surface of the folded polypeptide a reactive site has been engineered that is capable of catalyzing acyl-transfer reactions of reactive esters, The reactive site of KO-42 contains six histidine residues with perturbed pK(a) values. The pK(a)s of His-15, His-30, and His-34 are close to 5, whereas those of His-11, His-19, and His-26 are close to 7, with nonideal titration curves. The second-order rate constant for the KO-42 catalyzed hydrolysis of mono-p-nitrophenyl fumarate at pH 4.1 and 290 K is 0.1 M-1 s(-1), which is 1140 times larger than that of the 4-methylimidazole (4-MeIm) catalyzed reaction, 8.8 x 10(-5) M-1 s(-1). The second-order rate constant for the KO-42 catalyzed transesterification of mono-p-nitrophenyl fumarate to form the corresponding trifluoroethyl ester in 10 vol % trifluoroethanol at pH 4.1 and 290 K is 0.052 M-1 s(-1) which is 620 times larger than that of the 4-MeIm catalyzed reaction, 8.4 x 10(-5) M-1 s(-1). KO-42 catalyzes the corresponding reactions of other p-nitrophenyl esters with similar rate enhancements. At pH 4.1 in aqueous solution where the rate constant ratio k(2)(KO-42)/k(2)(4-MeIm) is larger than 10(3) the predominant reactive species of KO-42 have unprotonated histidines flanked by protonated histidines. The kinetic solvent isotope effect at pH 4.7 is 2.0 which shows that isotopic fractionation occurs in the transition state. The kinetic solvent isotope effect at pH 6.1 is 1.1 which shows that there is neither general acid-general base catalysis nor strong hydrogen bonding in the transition state of the rate-limiting reaction step at that pH. The results suggest that at low pH the dominant catalytic species functions through a mechanism where unprotonated nucleophilic histidines are flanked by protonated histidines that bind to one or both of the ester oxygens in the transition state.

  DOI：

  10.1021/ja970854s
• 作为产物：
  描述：

  对硝基苯酚 、 富马酸 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以62%的产率得到(E)-4-(4-nitrophenoxy)-4-oxobut-2-enoic acid
  参考文献：
  名称：

  设计，合成和构象分析3-环丁基氨基甲酰基乙内酰脲作为新型氢键驱动的通用拟肽†

  摘要：

  通过区域选择性多组分多米诺法，然后进行简单的偶联反应，合成了一组系统取代的3-环丁基氨基甲酰基乙内酰脲。计算，NMR研究和X射线分析表明，这些支架能够以类似的二级结构（如α-螺旋和β-turn）投射其侧链，并具有良好的焓和熵分布。

  DOI：

  10.1039/c7ob02680c

文献信息

• Nucleophilic and general acid catalysis at physiological pH by a designed miniature esteraseElectronic supplementary information (ESI) available: NOESY and TOCSY spectra; Table with NMR assignments and observed NOEs; complete set of kinetic data for Art-Est catalysis; mass spectrum of fumaryl-Art-Est intermediate; rate constants for the spontaneous and catalysed ester hydrolysis. See http://www.rsc.org/suppdata/ob/b4/b404730c/. Coordinates for the structure of Art-Est have been deposited in the Brookhaven Protein Data Bank, code 1v1d.
  作者：Andrew J. Nicoll、Rudolf K. Allemann

  DOI：10.1039/b404730c

  日期：——

  A 31-residue peptide (Art-Est) was designed to catalyse the hydrolysis of p-nitrophenyl esters through histidine catalysis on the solvent exposed face of the alpha-helix of bovine pancreatic polypeptide. NMR spectroscopy indicated that Art-Est adopted a stable 3-dimensional structure in solution. Art-Est was an efficient catalyst with second order rate constants of up to 0.050 M(-1) s(-1). The activity

  设计了一种31个残基的肽（Art-Est），通过组氨酸催化牛胰多肽α-螺旋的溶剂暴露面上催化对硝基苯酯的水解。NMR光谱表明Art-Est在溶液中采用了稳定的3维结构。Art-Est是一种有效的催化剂，其二级速率常数高达0.050 M（-1）s（-1）。Art-Est的活性是His-22亲核性提高的结果，由于与His-18和带正电的Arg-25和Arg-26相互作​​用，pK（a）值降低了5.5。 。质谱和NMR光谱证实，Art-Est催化的对硝基苯基酯水解是通过酰基酶中间体进行的。溶剂动力学同位素效应为1。图8表明酰基中间体之前的过渡态通过与His-18的质子化侧链的相互作用而稳定，并表明了与通常对天然酯酶观察到的反应机理相似的反应机理。涉及两个具有不同pK（a）值的组氨酸残基的反应导致反应速率对溶液pH的钟形依赖性。Art-Est的催化行为表明，所设计的微型酶可以通过透明的机制起作用，
• Bioactive stents for type II diabetics and methods for use thereof
  申请人：Carpenter W. Kenneth

  公开号：US20050238689A1

  公开（公告）日：2005-10-27

  The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

  本发明基于以下发现：在血管支架或其他植入式医疗设备上涂覆一种可生物降解的生物相容性聚合物，聚合物上附着一种生物配体，该生物配体可从循环血液中特异性捕获内皮细胞祖细胞（PECs），从而促进 II 型糖尿病患者健康内皮的内源性形成。在一个实施方案中，生物配体是一种能与 PECs 上的整合素受体特异性结合的多肽。本发明还提供了使用此类血管支架和其他植入装置促进 II 型糖尿病患者血管愈合的方法，例如在机械干预之后。
• Vaccine delivery compositions and methods of use
  申请人：Turnell G. William

  公开号：US20060188469A1

  公开（公告）日：2006-08-24

  The present invention provides synthetic vaccine delivery compositions based on polyester amide (PEA), polyester urethane (PEUR), and polyester urea (PEU) polymers for stimulating an immune response to a variety of pathogenic organisms and tumor cells in humans and other mammals. The vaccine delivery compositions are formulated as a liquid dispersion of polymer particles or molecules including class I or class II antigen peptides derived from organism or tumor cell proteins, which are taken up by antigen presenting cells of the mammal to induce an immune response in the mammal. Methods of inducing an immune response to the pathogenic organism or tumor cells in the invention compositions are also included.

  本发明提供了基于聚酯酰胺（PEA）、聚酯聚氨酯（PEUR）和聚酯脲（PEU）聚合物的合成疫苗递送组合物，用于激发人类和其他哺乳动物对各种病原体和肿瘤细胞的免疫反应。疫苗递送组合物配制成聚合物颗粒或分子的液态分散体，其中包括从生物体或肿瘤细胞蛋白质中提取的 I 类或 II 类抗原肽，它们被哺乳动物的抗原呈递细胞吸收，诱导哺乳动物产生免疫反应。还包括诱导对本发明组合物中的病原体或肿瘤细胞产生免疫反应的方法。
• Substrate Recognition and Saturation Kinetics in de Novo Designed Histidine-Based Four-Helix Bundle Catalysts
  作者：Kerstin S. Broo、Helena Nilsson、Jonas Nilsson、Lars Baltzer

  DOI：10.1021/ja980682e

  日期：1998.10.1

  Designed four-helix bundle proteins with reactive sites based on the cooperativity of HisH(+)-His pairs in helical sequences catalyze acyl-transfer reactions of p-nitrophenyl esters with large rate enhancements. The function of the HisH(+)-His site has been expanded by the introduction of flanking residues to provide recognition of substrate carboxylate and hydrophobic residues. The second-order rate constants for the MN 42 catalyzed hydrolysis of p-nitrophenyl acetate and of mono-p-nitrophenyl fumarate, under conditions of excess catalyst over substrate, in aqueous solution at pH 5.1 and 290 K are 0.030 M-1 s(-1) and 0.027 M-1 s(-1), respectively. The reactive site of MN-42 contains only histidine residues. The sequence of MNKR is the same as that of MN-42 except that one Lys and one Arg residue have been introduced in the adjacent helix to flank the HisH(+)-His site and the resulting second-order rate constants an 0.075 M-1 s(-1) and 0.135 M-1 s(-1). MNKR catalyzed hydrolysis of the fumarate follows saturation kinetics with a k(cat)/K-M of 0.17 M-1 s(-1) which is 230 times larger than the second-order rate constant of the 4-methyl imidazole catalyzed reaction. The second-order rate constants for the JNIII catalyzed hydrolysis of p-nitrophenyl acetate and of p-nitrophenyl valerate are 0.007 M-1 s(-1) and 0.097 M-1 s(-1), respectively, and binding of the aliphatic group increases the rate constant by more than one order of magnitude. Chiral recognition by de novo designed polypeptides has been demonstrated for the first time, and the hydrolysis of the p-nitrophenyl ester of D-norleucine has been catalyzed with a second-order rate constant that is twice as large as that of the L-norleucine ester.
• Versatility of helix-loop-helix catalysts - cooperative HisH<sup>+</sup>-His sites that span both helices
  作者：Jonas Nilsson、Kerstin S. Broo、Richard S. Sott、Lars Baltzer

  DOI：10.1139/cjc-77-5-6-990

  日期：——

  Peptides with 42 amino acid residues have been designed to fold into helix-loop-helix motifs that dimerize to form four-helix bundles and catalyze the hydrolysis of p-nitrophenyl esters. Their reactivities depend on nucleophilic and general-acid catalysis by cooperative HisH(+)-His pairs. The peptide catalyst MNV with the HisH(+)-His pair separated by three residues within the helical segment catalyzes the hydrolysis of p-nitrophenyl fumarate with a second-order rate constant of 0.034 M-1 s(-1) at pH 5.1 and 290 K. This i, i+3 site is a factor of three more efficient than the corresponding i, i+4 site. Helix-loop-helix peptides having histidines situated at opposing helices were designed and exhibited cooperative HisH(+)-His catalytic pairs. The peptide H11,34K hydrolyzed p-nitrophenyl acetate and p-nitrophenyl valerate with second-order rate constants of 0.044 and 0.15 M-1 s(-1), respectively, at pH 5.1 and 290 K, indicating that the hydrophobic substituent was recognized by the catalyst.