{3-propargyloxy-4-[2-(3,8,13-trimethoxy-7,12-bis[2-(4-hydryoxymethyl-2-methoxyphenoxy)ethoxy]-10,15-dihydro-5H-tribenzo[a,d,g]cyclononen-2-yloxy)ethoxy]phenyl}methanol | 914095-31-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {3-propargyloxy-4-[2-(3,8,13-trimethoxy-7,12-bis[2-(4-hydryoxymethyl-2-methoxyphenoxy)ethoxy]-10,15-dihydro-5H-tribenzo[a,d,g]cyclononen-2-yloxy)ethoxy]phenyl}methanol
• 英文别名: {3-propargyloxy-4-[2-(3,8,13-trimethoxy-7,12-bis[2-(4-hydroxymethyl-2-methoxyphenoxy)ethoxy]-10,15-dihydro-5H-tribenzo[a,d,g]cyclononen-2-yloxy)ethoxy]phenyl}methanol；[4-[2-[[12-[2-[4-(Hydroxymethyl)-2-methoxyphenoxy]ethoxy]-19-[2-[4-(hydroxymethyl)-2-prop-2-ynoxyphenoxy]ethoxy]-6,13,20-trimethoxy-5-tetracyclo[15.4.0.03,8.010,15]henicosa-1(21),3,5,7,10,12,14,17,19-nonaenyl]oxy]ethoxy]-3-methoxyphenyl]methanol；[4-[2-[[12-[2-[4-(hydroxymethyl)-2-methoxyphenoxy]ethoxy]-19-[2-[4-(hydroxymethyl)-2-prop-2-ynoxyphenoxy]ethoxy]-6,13,20-trimethoxy-5-tetracyclo[15.4.0.03,8.010,15]henicosa-1(21),3,5,7,10,12,14,17,19-nonaenyl]oxy]ethoxy]-3-methoxyphenyl]methanol
• CAS: 914095-31-1
• 化学式: C₅₆H₆₀O₁₅
• 分子量: 973.083
• InChiKey: UIZLOEVLZIVIJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  71
• 可旋转键数：
  25
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  171
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  {3-propargyloxy-4-[2-(3,8,13-trimethoxy-7,12-bis[2-(4-hydryoxymethyl-2-methoxyphenoxy)ethoxy]-10,15-dihydro-5H-tribenzo[a,d,g]cyclononen-2-yloxy)ethoxy]phenyl}methanol 在 高氯酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 48.0h， 以49%的产率得到monopropargyl-cryptophane-A
  参考文献：
  名称：

  WO2008/27162

  摘要：

  公开号：
• 作为产物：
  描述：

  12-[2-(4-hydroxymethyl-2-propargyloxyphenoxy)ethoxy]-3,8,13-trimethox-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene-2,7-diol 、 [4-(2-碘乙氧基)-3-甲氧基苯基]甲醇 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以80%的产率得到{3-propargyloxy-4-[2-(3,8,13-trimethoxy-7,12-bis[2-(4-hydryoxymethyl-2-methoxyphenoxy)ethoxy]-10,15-dihydro-5H-tribenzo[a,d,g]cyclononen-2-yloxy)ethoxy]phenyl}methanol
  参考文献：
  名称：

  Designing ¹²⁹Xe NMR Biosensors for Matrix Metalloproteinase Detection

  摘要：

  Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large nuclear magnetic signal of hyperpolarized Xe-129. Here, we report the first enzyme-responsive Xe-129 NMR biosensor. This compound was synthesized in 13 steps by attaching the consensus peptide substrate for matrix metalloproteinase-7 (MMP-7), an enzyme that is upregulated in many cancers, to the xenon-binding organic cage, cryptophane-A. The final coupling step was achieved on solid support in 80-92% yield via a copper (I)-catalyzed [3+2] cycloaddition. In vitro enzymatic cleavage assays were monitored by HPLC and fluorescence spectroscopy. The biosensor was determined to be an excellent substrate for MMP-7 (K-M = 43 mu M, V-max = 1.3 x 10(-8) M s(-1), k(cat)/K-M = 7200 M-1 s(-1)). Enzymatic cleavage of the tryptophan-containing peptide led to a dramatic decrease in Trp fluorescence, lambda(max) = 358 nm. Stern-Volmer analysis gave an association constant of 9000 +/- 1000 M-1 at 298 K between the cage and Trp-containing hexapeptide under enzymatic assay conditions. Most promisingly, Xe-129 NMR spectroscopy distinguished between the intact and cleaved biosensors with a 0.5 ppm difference in chemical shift. This difference most likely reflected a change in the electrostatic environment of Xe-129, caused by the cleavage of three positively charged residues from the C-terminus. This work provides guidelines for the design and application of new enzyme-responsive Xe-129 NMR biosensors.

  DOI：

  10.1021/ja0640501

文献信息

• 129Xe BIOSENSORS AND THEIR USE
  申请人：Dmochowski Ivan

  公开号：US20110104075A1

  公开（公告）日：2011-05-05

  This invention relates to enzyme-sensitive biosensors and methods and kits using the same. Specifically, the invention relates to methods, systems and kits for the detection of enzymes using the chemical shift observed in an isotope complexed to the biosensor resulting from a change in the biosensor as the result of the enzyme's activity.

  本发明涉及酶敏感生物传感器及其使用的方法和试剂盒。具体而言，本发明涉及使用同位素与生物传感器相结合所观察到的化学位移来检测酶的方法、系统和试剂盒，该化学位移是由于酶的活性导致生物传感器发生变化所致。
• US8470587B2
  申请人：——

  公开号：US8470587B2

  公开（公告）日：2013-06-25
• [EN] 129XE BIOSENSORS AND THEIR USE<br/>[FR] BIOCAPTEURS 129XE ET LEUR UTILISATION
  申请人：UNIV PENNSYLVANIA

  公开号：WO2008027162A2

  公开（公告）日：2008-03-06

  [EN] This invention relates to enzyme-sensitive biosensors and methods and kits using the same. Specifically, the invention relates to methods, systems and kits for the detection of enzymes using the chemical shift observed in an isotope complexed to the biosensor resulting from a change in the biosensor as the result of the enzyme's activity.
  [FR] L'invention concerne des biocapteurs sensibles aux enzymes, des procédés et des ensembles employant ces biocapteurs. L'invention concerne plus particulièrement des procédés, des systèmes et des ensembles de détection d'enzymes au moyen du décalage chimique observé dans un isotope complexé au biocapteur résultant d'un changement dans le biocapteur en résultat de l'activité de l'enzyme.
• WO2008/27162
  申请人：——

  公开号：——

  公开（公告）日：——
• Designing ¹²⁹Xe NMR Biosensors for Matrix Metalloproteinase Detection
  作者：Qian Wei、Garry K. Seward、P. Aru Hill、Brian Patton、Ivan E. Dimitrov、Nicholas N. Kuzma、Ivan J. Dmochowski

  DOI：10.1021/ja0640501

  日期：2006.10.1

  Xenon-129 biosensors offer an attractive alternative to conventional MRI contrast agents due to the chemical shift sensitivity and large nuclear magnetic signal of hyperpolarized Xe-129. Here, we report the first enzyme-responsive Xe-129 NMR biosensor. This compound was synthesized in 13 steps by attaching the consensus peptide substrate for matrix metalloproteinase-7 (MMP-7), an enzyme that is upregulated in many cancers, to the xenon-binding organic cage, cryptophane-A. The final coupling step was achieved on solid support in 80-92% yield via a copper (I)-catalyzed [3+2] cycloaddition. In vitro enzymatic cleavage assays were monitored by HPLC and fluorescence spectroscopy. The biosensor was determined to be an excellent substrate for MMP-7 (K-M = 43 mu M, V-max = 1.3 x 10(-8) M s(-1), k(cat)/K-M = 7200 M-1 s(-1)). Enzymatic cleavage of the tryptophan-containing peptide led to a dramatic decrease in Trp fluorescence, lambda(max) = 358 nm. Stern-Volmer analysis gave an association constant of 9000 +/- 1000 M-1 at 298 K between the cage and Trp-containing hexapeptide under enzymatic assay conditions. Most promisingly, Xe-129 NMR spectroscopy distinguished between the intact and cleaved biosensors with a 0.5 ppm difference in chemical shift. This difference most likely reflected a change in the electrostatic environment of Xe-129, caused by the cleavage of three positively charged residues from the C-terminus. This work provides guidelines for the design and application of new enzyme-responsive Xe-129 NMR biosensors.