(alpha1S,alpha4S,alpha8S)-alpha,alpha',alpha''-三[二[2-(1,1-二甲基乙氧基)-2-氧代乙基]氨基]-delta,delta',delta''-三氧代-1,4,8,11-四氮杂环十四烷-1,4,8-三戊酸1,4,8-三(1,1-二甲基乙基)酯 | 862778-56-1

• 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
• 中文名称: (alpha1S,alpha4S,alpha8S)-alpha,alpha',alpha''-三[二[2-(1,1-二甲基乙氧基)-2-氧代乙基]氨基]-delta,delta',delta''-三氧代-1,4,8,11-四氮杂环十四烷-1,4,8-三戊酸1,4,8-三(1,1-二甲基乙基)酯
• 英文名称: 5-{8,11-bis[4-bis(tert-butoxycarbonymethyl)amino-4-tert-butoxycarbonylbutyryl]-1,4,8,11-tetraazacyclotetradec-1-yl}-2-bis(tert-butoxycarbonylmethyl)amino-5-oxopentanoic acid tert-butyl ester
• 英文别名: cyclam-Glu-trisNTA-OtBu；tert-butyl (2S)-5-[4,8-bis[(4S)-4-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-5-[(2-methylpropan-2-yl)oxy]-5-oxopentanoyl]-1,4,8,11-tetrazacyclotetradec-1-yl]-2-[bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-5-oxopentanoate
• CAS: 862778-56-1
• 化学式: C₇₃H₁₂₉N₇O₂₁
• 分子量: 1440.86
• InChiKey: OAYGKFKKVVWTMW-VPMCDZTMSA-N

物化性质

• 熔点：
  >62°C (dec.)
• 沸点：
  1130.2±65.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  101
• 可旋转键数：
  45
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  319
• 氢给体数：
  1
• 氢受体数：
  25

反应信息

• 作为反应物：
  描述：

  (alpha1S,alpha4S,alpha8S)-alpha,alpha',alpha''-三[二[2-(1,1-二甲基乙氧基)-2-氧代乙基]氨基]-delta,delta',delta''-三氧代-1,4,8,11-四氮杂环十四烷-1,4,8-三戊酸1,4,8-三(1,1-二甲基乙基)酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以91%的产率得到2,2′,2″,2′″,2″″,2′″″-(((1,4,8,11-tetraazacyclotetradecane-1,4,8-triyl)tris(1-carboxy-4-oxobutane-4,1-diyl))tris(azantriyl))hexaacetic acid
  参考文献：
  名称：

  Hybridization of an Aβ-specific antibody fragment with aminopyrazole-based β-sheet ligands displays striking enhancement of target affinity

  摘要：

  一个带有His标签的抗体与NTA-β-折叠破坏剂结合，显示出对Aβ亲和力的显著增强。

  DOI：

  10.1039/c4ob02411g
• 作为产物：
  描述：

  2-bis(tert-butoxycarbonylmethyl)aminopentanedioic acid 1-tert-butyl ester 、 1,4,8,11-四氮杂环十四烷 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以79%的产率得到(alpha1S,alpha4S,alpha8S)-alpha,alpha',alpha''-三[二[2-(1,1-二甲基乙氧基)-2-氧代乙基]氨基]-delta,delta',delta''-三氧代-1,4,8,11-四氮杂环十四烷-1,4,8-三戊酸1,4,8-三(1,1-二甲基乙基)酯
  参考文献：
  名称：

  用于组氨酸标签蛋白的可切换识别的高亲和力接头

  摘要：

  我们渴望创建化学识别单元，以高亲和力和稳定性结合寡聚组氨酸标签，作为将光谱探针和其他功能元件选择性地连接到重组蛋白的工具。合成了几个包含 2-4 个次氮基三乙酸 (NTA) 部分的超分子实体，其中还包含一个氨基，荧光素作为灵敏的报告探针与之偶联。这些多价螯合剂头 (MCH)（称为 bis-、tris-和 tetrakis-NTA）的特征在于它们与六组氨酸 (H6) 和十组氨酸 (H10) 标记目标的相互作用。通过分析尺寸排阻色谱观察到随着NTA部分数量的增加，结合稳定性显着增加。通过等温滴定量热法测定的结合焓几乎随着螯合剂头和标签之间可能的配位键的数量增加而增加。然而，要获得完全相加的结合焓，需要寡聚组氨酸标签中大量过量的组氨酸。与单-NTA 相比，通过荧光去猝灭测量的 MCH/寡聚组氨酸复合物的解离动力学显示稳定性增加了 4 个数量级，并且对 tris-NTA 达到了亚纳摩尔亲和力。随着

  DOI：

  10.1021/ja050690c

文献信息

• The Scaffold Design of Trivalent Chelator Heads Dictates Affinity and Stability for Labeling His-tagged Proteins in vitro and in Cells
  作者：Karl Gatterdam、Eike F. Joest、Volker Gatterdam、Robert Tampé

  DOI：10.1002/anie.201802746

  日期：2018.9.17

  (MCHs) built on linear, cyclic, and dendritic scaffolds and compare these with regard to their binding affinity and stability for the labeling of cellular His‐tagged proteins. Furthermore, we describe a new approach for tracing cellular target proteins at picomolar probe concentrations in cells. Finally, we outline fundamental differences between the MCH scaffolds and define a cyclic trisNTA chelator that

  小型的化学/生物相互作用对在追踪蛋白质功能和细胞途径中高信噪比的相互作用中处于最前沿。但是，支架，连接子和螯合剂头的最佳设计仍然值得系统研究，以在体外尤其是细胞应用中获得最高的亲和力和动力学稳定性。我们在N的图书馆报告基于三硝基三乙酸（NTA）的多价螯合剂头（MCH）构建在线性，环状和树突状支架上，并就结合亲和力和对细胞His-tagged蛋白标记的稳定性进行比较。此外，我们描述了一种在皮摩尔探针浓度下追踪细胞靶蛋白的新方法。最后，我们概述了MCH支架之间的基本差异，并定义了一种环状tris NTA螯合剂，该螯合剂在所有报道的可逆，低分子量相互作用对中显示出最高的亲和力和动力学稳定性。
• Specific and Stable Fluorescence Labeling of Histidine-Tagged Proteins for Dissecting Multi-Protein Complex Formation
  作者：Suman Lata、Martynas Gavutis、Robert Tampé、Jacob Piehler

  DOI：10.1021/ja0563105

  日期：2006.2.1

  Labeling of proteins with fluorescent dyes offers powerful means for monitoring protein interactions in vitro and in live cells. Only a few techniques for noncovalent fluorescence labeling with well-defined localization of the attached dye are currently available. Here, we present an efficient method for site-specific and stable noncovalent fluorescence labeling of histidine-tagged proteins. Different fluorophores were conjugated to a chemical recognition unit bearing three NTA moieties (tris-NTA). In contrast to the transient binding of conventional mono-NTA, the multivalent interaction of tris-NTA conjugated fluorophores with oligohistidine-tagged proteins resulted in complex lifetimes of more than an hour. The high selectivity of tris-NTA toward cumulated histidines enabled selective labeling of proteins in cell lysates and on the surface of live cells. Fluorescence labeling by tris-NTA conjugates was applied for the analysis of a ternary protein complex in solution and on surfaces. Formation of the complex and its stoichiometry was studied by analytical size exclusion chromatography and fluorescence quenching. The individual interactions were dissected on solid supports by using simultaneous mass-sensitive and multicolor fluorescence detection. Using these techniques, formation of a 1:1:1 stoichiometry by independent interactions of the receptor subunits with the ligand was shown. The incorporation of transition metal ions into the labeled proteins upon labeling with tris-NTA fluorophore conjugates provided an additional sensitive spectroscopic reporter for detecting and monitoring protein-protein interactions in real time. A broad application of these fluorescence conjugates for protein interaction analysis can be envisaged.
• Identifying Modulators of Protein−Protein Interactions Using Photonic Crystal Biosensors
  作者：James T. Heeres、Seok-Ho Kim、Benjamin J. Leslie、Erich A. Lidstone、Brian T. Cunningham、Paul J. Hergenrother

  DOI：10.1021/ja907066r

  日期：2009.12.30

  Inhibitors and activators of protein-protein interactions are valuable as biological probes and medicinal agents but are often difficult to identify. Herein we describe a high-throughput assay, based upon photonic crystal (PC) biosensors, for the identification of modulators of protein-protein interactions. Through the use of a D-biotin-tris-NTA (BTN) hybrid compound, any His6-tagged protein can be immobilized on the surface of a PC biosensor. Binding of the bound protein to its cognate partner is detected via a shift in the peak wavelength value. We demonstrate this assay with three protein-protein pairs (caspase-9-XIAP, caspase-7-XIAP, FKBP12-FRB) and their small molecule modulators.