(2S,2'S,2''S)-2,2',2''-((2S,5S,8S,11S)-2,5,8,11-tetramethyl-10-((S)-1-oxo-1-((2-(pyridin-2yldithio)ethyl)amino)propan-2-yl)-1,4,7,10-tetraazacyclo-dodecane-1,4,7-triyl)tripropanoic acid | 1192364-56-9

• 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
• 英文名称: (2S,2'S,2''S)-2,2',2''-((2S,5S,8S,11S)-2,5,8,11-tetramethyl-10-((S)-1-oxo-1-((2-(pyridin-2yldithio)ethyl)amino)propan-2-yl)-1,4,7,10-tetraazacyclo-dodecane-1,4,7-triyl)tripropanoic acid
• 英文别名: (2S,2'S,2''S)-2,2',2''-((2S,5S,8S,11S)-2,5,8,11-tetramethyl-10-((S)-1-oxo-1-(2-(pyridin-2-yldisulfanyl)ethylamino)propan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)tripropanoic acid；M8-SPy；(S)-M8-SPy；(2S)-2-[(2S,5S,8S,11S)-7,10-bis[(1S)-1-carboxyethyl]-2,5,8,11-tetramethyl-4-[(2S)-1-oxo-1-[2-(pyridin-2-yldisulfanyl)ethylamino]propan-2-yl]-1,4,7,10-tetrazacyclododec-1-yl]propanoic acid
• CAS: 1192364-56-9
• 化学式: C₃₁H₅₂N₆O₇S₂
• 分子量: 684.922
• InChiKey: BVEXZTXAUQXVNC-CAQMSIDYSA-N

物化性质

• 溶解度：
  可微溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -3.7
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  217
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  氯化镝(III) 、 (2S,2'S,2''S)-2,2',2''-((2S,5S,8S,11S)-2,5,8,11-tetramethyl-10-((S)-1-oxo-1-((2-(pyridin-2yldithio)ethyl)amino)propan-2-yl)-1,4,7,10-tetraazacyclo-dodecane-1,4,7-triyl)tripropanoic acid 以 水 为溶剂， 以90%的产率得到[Dy(M8-SPy)]
  参考文献：
  名称：

  DOTA-M8: An Extremely Rigid, High-Affinity Lanthanide Chelating Tag for PCS NMR Spectroscopy

  摘要：

  A new lanthanide chelating tag (M8) for paramagnetic labeling of biomolecules is presented, which is based on an eight-fold, stereoselectively methyl-substituted DOTA that can be covalently linked to the host molecule by a single disulfide bond. The steric overcrowding of the DOTA scaffold leads to an extremely rigid, kinetically and chemically inert lanthanide chelator Its steric bulk restricts the motion of the tag relative to the host molecule. These properties result in very large pseudocontact shifts (>5 ppm) and residual dipolar couplings (>20 Hz) for Dy-M8 linked to ubiquitin, which are unprecedented for a small, single-point-attachment tag. Such large pseudocontact shifts should be well detectable even for larger proteins and distances beyond similar to 50 angstrom. Due to its exceptionally high stability and lanthanide affinity M8 can be used under extreme chemical or physical conditions, such as those applied for protein denaturation, or when it is undesirable that buffer or protein react with excess lanthanide ions.

  DOI：

  10.1021/ja903233w
• 作为产物：
  描述：

  在 茴香硫醚 、 水 、 三氟乙酸 作用下， 反应 5.0h， 以21.5 mg的产率得到(2S,2'S,2''S)-2,2',2''-((2S,5S,8S,11S)-2,5,8,11-tetramethyl-10-((S)-1-oxo-1-((2-(pyridin-2yldithio)ethyl)amino)propan-2-yl)-1,4,7,10-tetraazacyclo-dodecane-1,4,7-triyl)tripropanoic acid
  参考文献：
  名称：

  DOTA-M8: An Extremely Rigid, High-Affinity Lanthanide Chelating Tag for PCS NMR Spectroscopy

  摘要：

  A new lanthanide chelating tag (M8) for paramagnetic labeling of biomolecules is presented, which is based on an eight-fold, stereoselectively methyl-substituted DOTA that can be covalently linked to the host molecule by a single disulfide bond. The steric overcrowding of the DOTA scaffold leads to an extremely rigid, kinetically and chemically inert lanthanide chelator Its steric bulk restricts the motion of the tag relative to the host molecule. These properties result in very large pseudocontact shifts (>5 ppm) and residual dipolar couplings (>20 Hz) for Dy-M8 linked to ubiquitin, which are unprecedented for a small, single-point-attachment tag. Such large pseudocontact shifts should be well detectable even for larger proteins and distances beyond similar to 50 angstrom. Due to its exceptionally high stability and lanthanide affinity M8 can be used under extreme chemical or physical conditions, such as those applied for protein denaturation, or when it is undesirable that buffer or protein react with excess lanthanide ions.

  DOI：

  10.1021/ja903233w

文献信息

• Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies
  作者：Ana Christina L. Opina、Madeleine Strickland、Yong-Sok Lee、Nico Tjandra、R. Andrew Byrd、Rolf E. Swenson、Olga Vasalatiy

  DOI：10.1039/c5dt03210e

  日期：——

  prepared. The isomer ratio of SSSS-SSSS-M4DOTMA complexed with a series of lanthanide ions was carefully investigated using RP-HPLC and NMR. A square antiprismatic (SAP) configuration was exclusively observed for the early lanthanides, while the twisted square antiprismatic (TSAP) geometry was preferred as the lanthanide ion size decreases. The late lanthanides preferentially adopted the TSAP geometry. One

  一种刚性对称的聚甲基化1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（DOTA）配体，在四氮杂环和乙酸酯臂中均带有四个SSSS甲基（SSSS-SSSS -M4DOTMA）准备好了。使用RP-HPLC和NMR仔细研究了与一系列镧系元素离子络合的SSSS-SSSS -M4DOTMA的异构体比率。早期镧系元素仅观察到方形反棱柱（SAP）构型，而镧系元素离子尺寸减小时，扭曲方形反棱柱（TSAP）几何结构更可取。晚期镧系元素优先采用TSAP几何形状。悬垂臂之一被吡啶二硫基修饰（SSSS-SSSS-M8SPy）用于半胱氨酸连接，并显示出与母体化合物Ln- SSSS-SSSS -M4DOTMA相似的异构体趋势。共价连接到泛素S57C突变体显示共振，其强度与RP-HPLC观察到的异构体一致。此外，NOE实验结合量子化学计算已明确证明，Pr -SSSS-SSSS- M4DOTMA和Pr -SSSS-SSSS
• Gd(III) complexes for electron–electron dipolar spectroscopy: Effects of deuteration, pH and zero field splitting
  作者：Luca Garbuio、Kaspar Zimmermann、Daniel Häussinger、Maxim Yulikov

  DOI：10.1016/j.jmr.2015.08.009

  日期：2015.10

  Spectral parameters of Gd(III) complexes are intimately linked to the performance of the Gd(III)nitroxide or Gd(III)-Gd(III) double electron-electron resonance (DEER or PELDOR) techniques, as well as to that of relaxation induced dipolar modulation enhancement (RIDME) spectroscopy with Gd(III) ions. These techniques are of interest for applications in structural biology, since they can selectively detect site-to-site distances in biomolecules or biomolecular complexes in the nanometer range. Here we report relaxation properties, echo detected EPR spectra, as well as the magnitude of the echo reduction effect in Gd(III)-nitroxide DEER for a series of Gadolinium(III) complexes with chelating agents derived from tetraazacyclododecane. We observed that solvent deuteration does not only lengthen the relaxation times of Gd(III) centers but also weakens the DEER echo reduction effect. Both of these phenomena lead to an improved signal-to-noise ratios or, alternatively, longer accessible distance range in pulse EPR measurements. The presented data enrich the knowledge on paramagnetic Gd(III) chelate complexes in frozen solutions, and can help optimize the experimental conditions for most types of the pulse measurements of the electron-electron dipolar interactions. (C) 2015 Elsevier Inc. All rights reserved.
• DOTA-M8: An Extremely Rigid, High-Affinity Lanthanide Chelating Tag for PCS NMR Spectroscopy
  作者：Daniel Häussinger、Jie-rong Huang、Stephan Grzesiek

  DOI：10.1021/ja903233w

  日期：2009.10.21

  A new lanthanide chelating tag (M8) for paramagnetic labeling of biomolecules is presented, which is based on an eight-fold, stereoselectively methyl-substituted DOTA that can be covalently linked to the host molecule by a single disulfide bond. The steric overcrowding of the DOTA scaffold leads to an extremely rigid, kinetically and chemically inert lanthanide chelator Its steric bulk restricts the motion of the tag relative to the host molecule. These properties result in very large pseudocontact shifts (>5 ppm) and residual dipolar couplings (>20 Hz) for Dy-M8 linked to ubiquitin, which are unprecedented for a small, single-point-attachment tag. Such large pseudocontact shifts should be well detectable even for larger proteins and distances beyond similar to 50 angstrom. Due to its exceptionally high stability and lanthanide affinity M8 can be used under extreme chemical or physical conditions, such as those applied for protein denaturation, or when it is undesirable that buffer or protein react with excess lanthanide ions.