fluoroacetyl-CoA | 485-13-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: fluoroacetyl-CoA
• 英文别名: S-[2-[3-[[(2R)-4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethyl] 2-fluoroethanethioate
• CAS: 485-13-2
• 化学式: C₂₃H₃₇FN₇O₁₇P₃S
• 分子量: 827.569
• InChiKey: MXORLDKQFQCTLP-GRFIIANRSA-N

物化性质

• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -5.2
• 重原子数：
  52
• 可旋转键数：
  21
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  389
• 氢给体数：
  9
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  fluoroacetyl-CoA 在 His-tagged Streptomyces cattleya FlK thioesterase 作用下， 生成 辅酶 A
  参考文献：
  名称：

  Structural Basis for the Activity and Substrate Specificity of Fluoroacetyl-CoA Thioesterase FlK

  摘要：

  The thioesterase FlK from the fluoroacetate-producing Streptomyces cattleya catalyzes the hydrolysis of fluoroacetyl-coenzyme A. This provides an effective self-defense mechanism, preventing any fluoroacetyl-coenzyme A formed from being further metabolized to 4-hydroxy-trans-aconitate, a lethal inhibitor of the tricarboxylic acid cycle. Remarkably, FlK does not accept acetyl-coenzyme A as a substrate. Crystal structure analysis shows that FlK forms a dimer, in which each subunit adopts a hot dog fold as observed for type II thioesterases. Unlike other type II thioesterases, which invariably utilize either an aspartate or a glutamate as catalytic base, we show by site-directed mutagenesis and crystallography that FlK employs a catalytic triad composed of Thr(42), His(76), and a water molecule, analogous to the Ser/Cys-His-acid triad of type I thioesterases. Structural comparison of FlK complexed with various substrate analogues suggests that the interaction between the fluorine of the substrate and the side chain of Arg(120) located opposite to the catalytic triad is essential for correct coordination of the substrate at the active site and therefore accounts for the substrate specificity.

  DOI：

  10.1074/jbc.m110.107177
• 作为产物：
  描述：

  coenzyme A trilithium salt 、 sodium fluoroacetate 在 草酰氯 、 碳酸氢钠 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 0.05h， 生成 fluoroacetyl-CoA
  参考文献：
  名称：

  氟乙酰辅酶A特异性硫酯酶的结构和生化研究揭示了氟选择性的分子基础

  摘要：

  我们启动了一项广泛的计划，旨在了解酶系统中氟特异性的分子基础，在这种情况下，我们报告了对来自卡特兰链霉菌的氟乙酰辅酶 A (CoA) 特异性硫酯酶 (FlK) 的晶体学和生化研究。我们的数据表明，FlK 能够在体内保护其宿主免受氟乙酸盐毒性，并证明氟乙酰辅酶 A ( k cat / K M = 5 × 10 7 M -1 s -1 ) 和乙酰辅酶 A之间有 10 6倍的区别( k猫/ K M = 30 M −1s -1) 基于源自底物反应性和结合差异的单一氟取代。我们表明 Thr 42、Glu 50 和 His 76 是关键的催化残基，并确定了影响底物选择性的几个因素。我们建议 FlK 最大限度地减少与硫酯羰基的相互作用，导致对乙酰辅酶 A 结合的选择，这可以通过 T42S 和 T42C 突变体中新的 C=O 相互作用部分恢复。我们假设这些相互作用的损失由氟化底物结合在由盖子结构产生的疏水结合袋中的熵驱动力补偿，其中包含

  DOI：

  10.1021/bi101102u

文献信息

• [EN] LINKING AMINO ACID SEQUENCES, MANUFACTURING METHOD THEREOF, AND USE THEREOF<br/>[FR] SÉQUENCES D'ACIDES AMINÉS DE LIAISON, LEUR MÉTHODE DE FABRICATION ET LEUR UTILISATION
  申请人：UNIV TEMPLE

  公开号：WO2021163467A1

  公开（公告）日：2021-08-19

  This invention provides compositions comprising linked amino acid sequences, pharmaceutical compositions comprising linked amino acid sequences, and methods of making thereof. This invention also provides methods of delivering said compositions to subjects and methods of treating various disorders and diseases using the said compositions.

  本发明提供了包含连接氨基酸序列的组合物、包含连接氨基酸序列的药物组合物以及其制备方法。本发明还提供了将所述组合物递送至受试者的方法，以及使用所述组合物治疗各种疾病和障碍的方法。
• METHODS FOR THE SITE-SELECTIVE INTRODUCTION OF HALOGEN INTO NATURAL PRODUCTS
  申请人：CHANG Michelle C.Y.

  公开号：US20160201095A1

  公开（公告）日：2016-07-14

  Organohalides (e.g., organofluorides) represent a rapidly expanding proportion of molecules used in pharmaceuticals, diagnostics, agrochemicals, and materials. The present invention exploits the naturally occurring acetate condensation pathway as a means of introducing halogenated building blocks into natural product scaffolds. In an exemplary embodiment, the invention provides a pathway involving at least one polyketide synthase system and utilizes haloacetate or a haloacetate synthon (e.g., halomalonate) to incorporate an organohalide into the polyketide backbone in vitro. In an exemplary embodiment, the invention provides an analogous method for site-selective introduction of haloacetate or a synthon into polyketide products in vivo. The present invention expands the scope of existing chemical methods for producing halogenated natural product scaffolds such as complex halogenated natural products.

  有机卤化物（例如有机氟化物）代表了在制药、诊断、农业化学品和材料中使用的分子的快速扩展比例。本发明利用自然存在的醋酸酯缩合途径作为将卤代建筑块引入天然产物支架的手段。在一个示例实施方式中，该发明提供了一个涉及至少一个聚酮合成酶系统的途径，并利用卤代醋酸盐或卤代醋酸盐合成物（例如卤代马来酸盐）在体外将有机卤化物并入聚酮骨架中。在一个示例实施方式中，该发明提供了一种类似的方法，用于在体内选择性地引入卤代醋酸盐或合成物到聚酮产品中。本发明扩展了现有化学方法的范围，用于生产卤代天然产物支架，例如复杂的卤代天然产物。
• LABELLED CARBOXYLIC ACIDS AND THEIR USES IN MOLECULAR IMAGING
  申请人：Imperial Innovations Limited

  公开号：US20160095946A1

  公开（公告）日：2016-04-07

  The present invention pertains generally to the field of imaging compounds, and more specifically to certain 2,2-dialkyl radionuclide-labelled carboxylic acids suitable for PEWT, SPECT and/or DNP imaging. Also described are uses of such compounds in the imaging of, inter alia, cancer tumors, metastasis, Alzheimer's disease and multiple sclerosis.

  本发明一般涉及成像化合物领域，更具体地涉及某些适用于PET、SPECT和/或DNP成像的2,2-二烷基放射性标记的羧酸。还描述了这些化合物在成像癌瘤、转移、阿尔茨海默病和多发性硬化等方面的用途。
• Heterologous pathway to produce terpenes
  申请人：The Regents of the University of California

  公开号：US10167488B2

  公开（公告）日：2019-01-01

  Cells comprising a heterologous metabolic pathway are configured to produce a terpene product containing non-multiples of five carbon, particularly wherein the pathway comprises heterologous Lepidoptera insect juvenile hormone biosynthetic pathway enzymes of the insect's mevalonate pathway.

  包含异源代谢途径的细胞被配置为生产含有非五碳倍数的萜烯产品，特别是其中的途径包含昆虫甲羟戊酸途径的异源鳞翅目昆虫幼虫激素生物合成途径酶。
• Methods for making chemoautotrophic cells by engineering an energy conversion pathway and a carbon fixation pathway
  申请人：Ginkgo BioWorks, Inc.

  公开号：US10801045B2

  公开（公告）日：2020-10-13

  The present disclosure identifies pathways, mechanisms, systems and methods to confer chemoautotrophic production of carbon-based products of interest, such as sugars, alcohols, chemicals, amino acids, polymers, fatty acids and their derivatives, hydrocarbons, isoprenoids, and intermediates thereof, in organisms such that these organisms efficiently convert inorganic carbon to organic carbon-based products of interest using inorganic energy, such as formate, and in particular the use of organisms for the commercial production of various carbon-based products of interest.

  本公开内容确定了在生物体内赋予化能自养生产感兴趣的碳基产品（如糖、醇、化学品、氨基酸、聚合物、脂肪酸及其衍生物、碳氢化合物、异肾上腺素及其中间体）的途径、机制、系统和方法，从而使这些生物体利用无机能源（如甲酸盐）有效地将无机碳转化为感兴趣的有机碳基产品，特别是利用生物进行各种感兴趣的碳基产品的商业化生产。