12-叠氮十二酸,12-AZIDO-DODECANOICACID | 80667-36-3

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 12-叠氮十二酸,12-AZIDO-DODECANOICACID
• 英文名称: 12-azidododecanoic acid
• CAS: 80667-36-3
• 化学式: C₁₂H₂₃N₃O₂
• 分子量: 241.334
• InChiKey: HYSGAVCDGKGYSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  17
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  51.7
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

叠氮肉豆蔻酸是一种含有叠氮基的点击化学试剂，可应用于简单的两步标记与检测技术，用于鉴定和表征翻译后肉豆蔻酸化的蛋白质。

反应信息

• 作为反应物：
  描述：

  12-叠氮十二酸,12-AZIDO-DODECANOICACID 在 吡啶 、 2-巯基吡啶 、 nitrosonium tetrafluoroborate 、 三乙胺 、 tin(ll) chloride 、 三乙基膦 作用下， 以 四氯化碳 、 乙腈 、 苯 为溶剂， 生成 氧杂环十三烷-2-酮
  参考文献：
  名称：

  从叠氮酸到大内酰胺和大内酯

  摘要：

  据报道，有一种新方法可以在高稀释条件下，通过硫酯的形成，叠氮化物的原位还原和环化作用，将叠氮基酸转化为内酰胺。由于已经证明大内酰胺向大内酯的定量转化是可行的，因此这导致了间接的替代大内酯化过程。

  DOI：

  10.1039/c39880000270
• 作为产物：
  描述：

  12-羟基十二酸 在 sodium hydroxide 、 sodium azide 、 三乙胺 、 乙酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 12-叠氮十二酸,12-AZIDO-DODECANOICACID
  参考文献：
  名称：

  Chemical Probes for the Rapid Detection of Fatty-Acylated Proteins in Mammalian Cells

  摘要：

  The attachment of lipids onto proteins modulates the activity of proteins in many biological settings. The analysis of protein lipidation, however, is challenging due to the relatively few methods for the detection of lipid-modified proteins. Here we describe the synthesis of omega-azido-fatty acids as non-radioactive chemical probes for the rapid visualization of fatty-acylated proteins in mammalian cells. Following metabolic installation of the omega-azido-fatty acids onto target proteins by cellular enzymes, fatty-acylated proteins are selectively biotinylated with a phosphine-biotin reagent via the Staudinger ligation and visualized by streptavidin blotting. Depending on the chain length of the omega-azido-fatty acids, N-myristoylated and S-palmitoylated proteins can be visualized selectively in cell lysates and on specific proteins. These chemical probes provide new tools to analyze fatty acylation of proteins in living cells.

  DOI：

  10.1021/ja0685001

文献信息

• Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis
  作者：Marzena Baran、Kimberly D. Grimes、Paul A. Sibbald、Peng Fu、Helena I.M. Boshoff、Daniel J. Wilson、Courtney C. Aldrich

  DOI：10.1016/j.ejmech.2020.112408

  日期：2020.9

  biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and

  结核分枝杆菌( Mtb ) 的脂质代谢依赖 34 种脂肪酸腺苷酸化酶 (FAdDs)，可分为两类：参与脂质和胆固醇分解代谢的脂肪酰基辅酶 A 连接酶 (FACL) 和长链脂肪酰基-AMP 连接酶 (FAAL) ) 参与Mtb 中发现的许多必需和赋予毒力的脂质的生物合成。许多 FACL 的精确生化作用仍不清楚，而功能非冗余的 FAAL 则更好理解。这里，我们描述的5'-系统调查ö - [ ñ - （链烷酰基）氨磺酰基]腺苷（烷酰基一denosine米ONO小号ulFAa href=https://www.molaid.com/MS_77914 target="_blank">AMate, alkanoyl-AMS) 类似物作为潜在的多靶点 FAdD 抑制剂，因为它们具有抗结核活性和对代表性 FAAL 和 FACL 酶的生化选择性。我们鉴定了几种有效的化合物，包括 12-叠氮十二烷酰基-AMS 28、11-苯氧基十一烷酰基-AMS 32和壬氧基乙酰基-AMS 36，其对结核分枝杆菌的最小抑制浓度 (MIC)范围为
• [EN] BIFUNCTIONAL COMPOUNDS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS BIFONCTIONNELS POUR LE TRAITEMENT DU CANCER
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021083949A1

  公开（公告）日：2021-05-06

  The invention provides bifunctional compounds of formula (I) or a pharmaceutically acceptable salt thereof. Formula (I). The compounds cause the degradation of SMARCA2 via the targeted ubiquination of SMARCA2 protein and subsequent proteasomal degradation and are thus useful for the treatment of cancer. The targeting ligand is of formula (TL).

  该发明提供了式（I）的双功能化合物或其药用可接受的盐。式（I）。这些化合物通过靶向泛素化SMARCA2蛋白并随后的蛋白酶体降解来导致SMARCA2的降解，因此对于癌症的治疗是有用的。靶向配体的化学式为（TL）。
• Modified N-acyl-homoserine lactones as chemical probes for the elucidation of plant–microbe interactions
  作者：Heike Thomanek、Sebastian T. Schenk、Elke Stein、Karl-Heinz Kogel、Adam Schikora、Wolfgang Maison

  DOI：10.1039/c3ob41215f

  日期：——

  Gram-negative bacteria often use N-acyl-homoserine lactones (AHLs) as signal molecules to monitor their local population densities and to regulate gene-expression in a process called “Quorum Sensing” (QS). This cell-to-cell communication allows bacteria to adapt to environmental changes and to behave as multicellular communities. QS plays a key role in both bacterial virulence towards the host and symbiotic interactions with other organisms. Plants also perceive AHLs and respond to them with changes in gene expression or modifications in development. Herein, we report the synthesis of new AHL-derivatives for the investigation and identification of AHL-interacting proteins. We show that our new compounds are still recognised by different bacteria and that a novel biotin-tagged-AHL derivative interacts with a bacterial AHL receptor.

  革兰氏阴性细菌常利用N-酰基高丝氨酸内酯（AHLs）作为信号分子，监测其局部种群密度，并通过一种称为“群体感应”（Quorum Sensing，简称QS）的过程调控基因表达。这种细胞间通讯使细菌能适应环境变化，表现为多细胞社群行为。QS在细菌对宿主的毒力以及其他生物的共生相互作用中发挥关键作用。植物也能感知AHLs，并以基因表达变化或发育改变来响应它们。在此，我们报道了新型AHL衍生物的合成，用于调查和鉴定AHL相互作用蛋白。我们展示，我们的新化合物仍被不同细菌识别，且一种新型生物素标记的AHL衍生物能与细菌的AHL受体相互作用。
• Functional synthetic molecules and macromolecules for gene delivery
  申请人：Grinstaff W. Mark

  公开号：US20060241071A1

  公开（公告）日：2006-10-26

  The present invention describes a synthetic non-viral vector composition for gene therapy and the use of such compositions for in vitro, ex vivo and/or in vivo transfer of genetic material. The invention proposes a pharmaceutical composition containing 1) a non-cationic amphiphilic molecule or macromolecule and its use for delivery of nucleic acids or 2) a cationic amphiphilic molecule or macromolecule that transforms from a cationic entity to an anionic, neutral, or zwitterionic entity by a chemical, photochemical, or biological reaction and its use for delivery of nucleic acids. Moreover this invention describes the use of these non-viral vector compositions in conjunction with a surface to mediate the delivery of nucleic acids. An additional embodiment is the formation of a hydrogel with these compositions and the use of this hydrogel for the delivery of genetic material. A further embodiment of this invention is the use of a change in ionic strength for the delivery of genetic material.

  本发明描述了一种用于基因治疗的合成非病毒载体组合，以及这种组合在体外、体内和/或体外转移遗传物质中的应用。该发明提出了一种包含1）非阳离子性两性分子或大分子的药物组合物及其用于传递核酸或2）由化学、光化学或生物反应从阳离子实体转变为阴离子、中性或带电离子实体的两性阳离子分子或大分子的药物组合物，以及其用于核酸传递。此外，本发明描述了这些非病毒载体组合物与表面结合以介导核酸传递的应用。另一实施例是使用这些组合物形成水凝胶，并利用该水凝胶传递遗传物质。本发明的另一实施例是利用离子强度变化传递遗传物质。
• Mapping Calcium-Sensitive Regions in the Neuronal Calcium Sensor GCAP2 by Site-Specific Fluorescence Labeling
  作者：Stefan Sulmann、Melanie Wallisch、Alexander Scholten、Jens Christoffers、Karl-Wilhelm Koch

  DOI：10.1021/acs.biochem.6b00005

  日期：2016.5.10

  Myristoylation of most neuronal calcium sensor proteins, a group of EF-hand calcium-binding proteins mainly expressed in neuronal tissue, can have a strong impact on protein dynamics and functional properties. Intracellular oscillations of the free Ca2+ concentration can trigger conformational changes in Ca2+ sensors. The position and possible movements of the myristoyl group in the photoreceptor cell-specific Ca2+ sensor GCAP2 are not well-defined but appear to be different from those of the highly homologous cognate GCAP1. We designed and applied a new group of diaminoterephthalate-derived fluorescent probes to label GCAP2 at a covalently attached 12-azido-dodecanoic acid (a myristoyl substitute) and at cysteine residues in critical positions. Fluorescence emission of dye-labeled GCAP2 decreased when going from low (10–9 M) to high [Ca2+] (10–3 M), reaching a half-maximal effect of fluorescence emission at 0.44 ± 0.07 μM. The modified acyl group can therefore monitor changes in the protein conformation during binding and dissociation of Ca2+ in the physiological range of free [Ca2+]. However, fluorescence quenching studies showed that the dye-acyl chain was shielded from the quencher by an adjacent polypeptide region. Further probing three cysteine positions (C35, C111, and C131) by dye labeling revealed that all positions were also sensitive to a change in [Ca2+], but only one (C131) was sensitive to a change in [Mg2+]. We suggest a scenario during illumination of the photoreceptor cell in which Ca2+ dissociates first from low and medium affinity binding sites. These steps are sensed by dyes in cysteines at positions 35 and 111. Release of Ca2+ from high affinity sites is sensed by regions adjacent to the dye-labeled fatty acid and involves the critical conformational change leading to activating guanylate cyclase.

  大多数神经钙传感蛋白的肉豆蔻酰化，一组主要在神经组织中表达的EF-Hand钙结合蛋白，能够对蛋白质的动态特性和功能属性产生强烈影响。细胞内自由Ca2+浓度的振荡可以触发钙传感器的构象变化。光感受器细胞特异性钙传感器GCAP2中肉豆蔻酰基的位置及其可能的运动尚不明确，但似乎与高度同源的GCAP1有所不同。我们设计并应用了一组新的取自二氨基对苯二甲酸的荧光探针，以在一个共价结合的12-叠氮-十二烷酸（肉豆蔻酰替代物）和关键位置的半胱氨酸残基上标记GCAP2。当[Ca2+]从低（10–9 M）增加到高（10–3 M）时，染料标记的GCAP2的荧光发射减少，在0.44 ± 0.07 μM时达到半最大荧光发射效果。因此，修饰的酰基可以监测在自由[Ca2+]生理范围内结合和解离Ca2+时蛋白质构象的变化。然而，荧光猝灭研究表明，染料-酰基链被邻近的多肽区域遮蔽，未受到猝灭剂的影响。通过染料标记进一步探测三个半胱氨酸位置（C35、C111和C131）显示，所有位置对[Ca2+]的变化都敏感，但仅有一个（C131）对[Mg2+]的变化敏感。我们建议在光照射光受体细胞时的一个情景，即Ca2+先从低亲和力和中亲和力结合位点解离。这些步骤通过在位置35和111的半胱氨酸中的染料被感知。来自高亲和力位点的Ca2+释放则由靠近染料标记的脂肪酸的区域感知，并涉及导致激活鸟苷酸环化酶的关键构象变化。