L-malate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: L-malate
• 英文别名: malate；(S)-malate；(2S)-2-hydroxybutanedioate
• 化学式: C₄H₄O₅
• 分子量: 132.073
• InChiKey: BJEPYKJPYRNKOW-REOHCLBHSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  L-malate 在 还原型辅酶Ⅰ 、 malate dehydrogenase 作用下， 生成 2-氧代丁二酸
  参考文献：
  名称：

  Identification of Fumarate Hydratase Inhibitors with Nutrient-Dependent Cytotoxicity

  摘要：

  Development of cell-permeable small molecules that target enzymes involved in energy metabolism remains important yet challenging. We describe here the discovery of a new class of compounds with a nutrient-dependent cytotoxicity profile that arises from pharmacological inhibition of fumarate hydratase (also known as fumarase). This finding was enabled by a high-throughput screen of a diverse chemical library in a panel of human cancer cell lines cultured under different growth conditions, followed by subsequent structure-activity optimization and target identification. While the highest cytotoxicity was observed under low glucose concentrations, the antiproliferative activities and inhibition of oxygen consumption rates in cells were distinctly different from those displayed by typical inhibitors of mitochondrial oxidative phosphorylation. The use of a photoaffinity labeling strategy identified fumarate hydratase as the principal pharmacological target. Final biochemical studies confirmed dose-dependent, competitive inhibition of this enzyme in vitro, which was fully consistent with the initially observed growth inhibitory activity. Our work demonstrates how the phenotypic observations combined with a successful target identification strategy can yield a useful class of pharmacological inhibitors of an enzyme involved in the operation of tricarboxylic acid cycle.

  DOI：

  10.1021/ja5101257
• 作为产物：
  描述：

  富马酸酯(2-) 在 fumarate hydratase 、 水 作用下， 生成 L-malate
  参考文献：
  名称：

  Identification of Fumarate Hydratase Inhibitors with Nutrient-Dependent Cytotoxicity

  摘要：

  Development of cell-permeable small molecules that target enzymes involved in energy metabolism remains important yet challenging. We describe here the discovery of a new class of compounds with a nutrient-dependent cytotoxicity profile that arises from pharmacological inhibition of fumarate hydratase (also known as fumarase). This finding was enabled by a high-throughput screen of a diverse chemical library in a panel of human cancer cell lines cultured under different growth conditions, followed by subsequent structure-activity optimization and target identification. While the highest cytotoxicity was observed under low glucose concentrations, the antiproliferative activities and inhibition of oxygen consumption rates in cells were distinctly different from those displayed by typical inhibitors of mitochondrial oxidative phosphorylation. The use of a photoaffinity labeling strategy identified fumarate hydratase as the principal pharmacological target. Final biochemical studies confirmed dose-dependent, competitive inhibition of this enzyme in vitro, which was fully consistent with the initially observed growth inhibitory activity. Our work demonstrates how the phenotypic observations combined with a successful target identification strategy can yield a useful class of pharmacological inhibitors of an enzyme involved in the operation of tricarboxylic acid cycle.

  DOI：

  10.1021/ja5101257
• 作为试剂：
  描述：

  (R)-(+)-3-甲基环己酮 在 recombinant short-chain dehydrogenase/reductase from Asparagus officinalis 、 烟酰胺腺嘌呤双核苷酸磷酸盐 、 L-malate 、 manganese(ll) chloride 、 malate dehydrogenase 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以60%的产率得到
  参考文献：
  名称：

  利用短链脱氢酶/还原酶的催化多样性：具有扩展的亚胺底物范围的植物的多种酶

  摘要：

  一种酶，具有三种活性：植物SDR诺马曲啶还原酶（NR）在生物碱生物合成中充当烯酮还原酶。在这里，我们表明NR接受不同的亚胺化合物，并具有酮还原酶活性。以NR为模板，我们确定了一种新型的减少亚胺的SDR。

  DOI：

  10.1002/cbic.201800291

文献信息

• Synthesis of alanine-based colorimetric sensors and enantioselective recognition of aspartate and malate anions
  作者：Wei-Chi Lin、Yu-Ping Tseng、Chi-Yung Lin、Yao-Pin Yen

  DOI：10.1039/c1ob05135k

  日期：——

  Two chiral colorimetric sensors (1,2) were synthesized and characterized by spectroscopic techniques and their enantioselective recognition of chiral dicarboxylic anions (D/L-aspartate and D/L-malate) was examined by UV-vis and 1H NMR spectroscopy. Interaction of the receptors 1 and 2 with the enantiomers of aspartate or malate caused different color changes, and they act as optical chemosensors for

  合成了两个手性比色传感器（1,2），并通过光谱技术对其进行了表征，并通过紫外可见光谱和1 H NMR光谱对它们的手性二羧酸阴离子（D / L-天冬氨酸和D / L-苹果酸）进行对映选择性识别。受体的相互作用1和2与天冬氨酸或苹果酸的对映异构体不同而引起的颜色变化，以及它们作为光学化学传感器用于识别d天冬氨酸与大号天冬氨酸和d -苹果与大号-苹果。受体1对天冬氨酸阴离子具有高对映选择性结合[ KA （D） / KA （L） = 12.15]。
• NAD-malic enzymes of <i>Arabidopsis thaliana</i> display distinct kinetic mechanisms that support differences in physiological control
  作者：Marcos A. Tronconi、Mariel C. Gerrard Wheeler、Verónica G. Maurino、María F. Drincovich、Carlos S. Andreo

  DOI：10.1042/bj20100497

  日期：2010.9.1

  The Arabidopsis thaliana genome contains two genes encoding NAD-MEs [NAD-dependent malic enzymes; NAD-ME1 (TAIR accession number At4G13560) and NAD-ME2 (TAIR accession number At4G00570)]. The encoded proteins are localized to mitochondria and assemble as homo- and hetero- dimers in vitro and in vivo. In the present work, the kinetic mechanisms of NAD-ME1 and -ME2 homodimers and NAD-MEH (NAD-ME heterodimer) were studied as an approach to understand the contribution of these enzymes to plant physiology. Product-inhibition and substrate-analogue analyses indicated that NAD-ME2 follows a sequential ordered Bi-Ter mechanism, NAD being the leading substrate followed by L-malate. On the other hand, NAD-ME1 and NAD-MEH can bind both substrates randomly. However, NAD-ME1 shows a preferred route that involves the addition of NAD first. As a consequence of the kinetic mechanism, NAD-ME1 showed a partial inhibition by L-malate at low NAD concentrations. The analysis of a protein chimaeric for NAD-ME1 and -ME2 indicated that the first 176 amino acids are associated with the differences observed in the kinetic mechanisms of the enzymes. Furthermore, NAD-ME1, -ME2 and -MEH catalyse the reverse reaction (pyruvate reductive carboxylation) with very low catalytic activity, supporting the notion that these isoforms act only in L-malate oxidation in plant mitochondria. The different kinetic mechanism of each NAD-ME entity suggests that, for a metabolic condition in which the mitochondrial NAD level is low and the L-malate level is high, the activity of NAD-ME2 and/or -MEH would be preferred over that of NAD-ME1.

  拟南芥基因组包含两个编码 NAD-MEs [NAD 依赖性苹果酸酶；NAD-ME1（TAIR登录号 At4G13560）和 NAD-ME2（TAIR登录号 At4G00570）]的基因。编码的蛋白定位于线粒体，在体外和体内以同源和异源二聚体的形式组装。本研究对 NAD-ME1 和 -ME2 同源二聚体以及 NAD-MEH（NAD-ME 异源二聚体）的动力学机制进行了研究，以了解这些酶对植物生理学的贡献。产物抑制和底物-类似物分析表明，NAD-ME2 遵循有序双三聚体机制，NAD 是主要底物，其次是 L-苹果酸。另一方面，NAD-ME1 和 NAD-MEH 可以随机结合两种底物。不过，NAD-ME1 显示出一种优先路线，即首先加入 NAD。由于这种动力学机制，NAD-ME1 在 NAD 浓度较低时受到 L-苹果酸的部分抑制。对 NAD-ME1 和 -ME2 嵌合蛋白的分析表明，前 176 个氨基酸与观察到的酶的动力学机制差异有关。此外，NAD-ME1、-ME2 和 -MEH 催化反向反应（丙酮酸还原羧化）的催化活性很低，这支持了这些异构体只在植物线粒体中起 L-苹果酸氧化作用的观点。每种 NAD-ME 实体不同的动力学机制表明，在线粒体 NAD 含量低而 L-苹果酸含量高的代谢条件下，NAD-ME2 和/或 -MEH 的活性优于 NAD-ME1 的活性。
• Amonafide salts
  申请人：Xanthus Life Sciences, Inc.

  公开号：US20040132763A1

  公开（公告）日：2004-07-08

  Disclosed is a salt of amonafide or amonafide analogs represented Structural Formula (I): 1 R1 is —(CH 2 ) n N + HR3R4 X − or R1 is —(CH 2 ) n N + HR3R4 X − or —(CH 2 ) n NR3R4 when R2 is —N + HR6R7. R2 is —OR5, halogen, —NR6R7, —N + HR6R7 X −, sulphonic acid, nitro, —NR5COOR5, —NR5COR5 or —OCOR5; R3 and R4 are independently H, C1-C4 alkyl group or, taken together with the nitrogen atom to which they are bonded, a non-aromatic nitrogen-containing heterocyclic group; each R5 is independently —H or a C1-C4 alkyl group; R6 and R7 are independently H, C1-C4 alkyl group or, taken together with the nitrogen atom to which they are bonded, a non-aromatic nitrogen-containing heterocyclic group; n is an integer from 0-3; and X − is the carboxylate anion of an organic carboxylic acid compound. Also disclosed are methods of preparing certain compounds represented by Structural Formula (I).

  本文揭示了一种氨咪非德盐或氨咪非德类似物的盐，其结构式表示为（I）：其中1R1为—（CH2）nN+HR3R4 X−或R1为—（CH2）nN+HR3R4 X−或—（CH2）nNR3R4，当R2为—N+HR6R7时。R2为—OR5，卤素，—NR6R7，—N+HR6R7 X−，磺酸，硝基，—NR5COOR5，—NR5COR5或—OCOR5；R3和R4独立地为H，C1-C4烷基或与它们连接的氮原子一起形成非芳香氮杂环基团；每个R5独立地为—H或C1-C4烷基；R6和R7独立地为H，C1-C4烷基或与它们连接的氮原子一起形成非芳香氮杂环基团；n为0-3的整数；X−是有机羧酸化合物的羧酸根阴离子。本文还揭示了制备某些结构式（I）化合物的方法。
• Immobilized intracellular enzymes
  申请人：Novo Industri A/S

  公开号：US04288552A1

  公开（公告）日：1981-09-08

  Intracellular glutaraldehyde sensitive enzymes are immobilized by reacting microbial cell material with glutaraldehyde in the presence of a polyamine which is preferably a branched polyethylene imine.

  细胞内对戊二醛敏感的酶通过在微生物细胞物质中加入多胺（最好是分支聚乙烯亚胺）的存在下，与戊二醛反应而被固定。
• Genetically Modified Cyanobacteria for the Production of Ethanol
  申请人：Woods R. Paul

  公开号：US20100068776A1

  公开（公告）日：2010-03-18

  The invention provides novel compositions of matter for the production of ethanol from carbon dioxide and water. Particularly, the invention provides photoautotrophic organisms having a first and second genetic modification, wherein the first genetic modification improves the ethanol production from organisms having the second genetic modification.

  本发明提供了一种从二氧化碳和水制备乙醇的新型物质组成。特别地，本发明提供了具有第一和第二基因修饰的光自养生物，其中第一基因修饰改善了具有第二基因修饰的生物体的乙醇产量。