E-TOCA | 1310573-41-1

• 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
• 英文名称: E-TOCA
• 英文别名: deamino-Pra-D-Phe-Cys(1)-Tyr-D-Trp-Lys-Thr-Cys(1)-Thr-OH；(2S,3R)-2-[[(4R,7S,10S,13R,16S,19R)-10-(4-aminobutyl)-7-[(1R)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1H-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-[[(2R)-2-(pent-4-ynoylamino)-3-phenylpropanoyl]amino]-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]amino]-3-hydroxybutanoic acid
• CAS: 1310573-41-1
• 化学式: C₅₄H₆₈N₁₀O₁₃S₂
• 分子量: 1129.33
• InChiKey: XMQOGEPZTMJCRB-CFOWPXFQSA-N

物化性质

• 沸点：
  1566.5±65.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  79
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  423
• 氢给体数：
  14
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2-[18F]fluoroethylazide 、 E-TOCA 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 disodium 4-[7-(4-sulfonatophenyl)-1,10-phenanthrolin-4-yl]benzenesulfonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.5h， 以51%的产率得到FETE-TOCA
  参考文献：
  名称：

  Synthesis and in vitro evaluation of [18F]fluoroethyl triazole labelled [Tyr3]octreotate analogues using click chemistry

  摘要：

  A novel class of alkyne linked [Tyr(3)]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [F-18]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr(3)]octreotate analogues, G-TOCA (3a) and beta AG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [F-18]2-fluoroethyl triazole linked [Tyr(3)]octreotate analogues FET-G-TOCA (3b) and FET-beta AG-TOCA (5b) under mild conditions and with short synthesis times (5 min at 20 degrees C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-beta AG-TOCA have high affinity for the somatostatin receptor with IC50 of 4.0 +/- 1.4, and 1.6 +/- 0.2 nM, respectively. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.016
• 作为产物：
  描述：

  H-D-Phe-Cys(Acm)-Tyr(tBu)-D-Trp-(Boc)-Lys(Boc)-Thr(tBu)-Cys(Acm)-Thr(tBu)-resin 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 生成 E-TOCA
  参考文献：
  名称：

  Quantitative Evaluation of Bioorthogonal Chemistries for Surface Functionalization of Nanoparticles

  摘要：

  We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.

  DOI：

  10.1021/bc3005057

文献信息

• Quantitative Evaluation of Bioorthogonal Chemistries for Surface Functionalization of Nanoparticles
  作者：Lise N. Feldborg、Rasmus I. Jølck、Thomas L. Andresen

  DOI：10.1021/bc3005057

  日期：2012.12.19

  We present here a highly efficient and chemoselective liposome functionalization method based on oxime bond formation between a hydroxylamine and an aldehyde-modified lipid component. We have conducted a systematic and quantitative comparison of this new approach with other state-of-the-art conjugation reactions in the field. Targeted liposomes that recognize overexpressed receptors or antigens on diseased cells have great potential in therapeutic and diagnostic applications. However, chemical modifications of nanoparticle surfaces by postfunctionalization approaches are less effective than in solution and often not high-yielding. In addition, the conjugation efficiency is often challenging to characterize and therefore not addressed in many reports. We present here an investigation of PEGylated liposomes functionalized with a neuroendocrine tumor targeting peptide (TATE), synthesized with a variety of functionalities that have been used for surface conjugation of nanoparticles. The reaction kinetics and overall yield were quantified by HPLC. Reactions were conducted in solution as well as by postfunctionalization of liposomes in order to study the effects of steric hindrance and possible affinity between the peptide and the liposome surface. These studies demonstrate the importance of choosing the correct chemistry in order to obtain a quantitative surface functionalization of liposomes.
• Synthesis and in vitro evaluation of [18F]fluoroethyl triazole labelled [Tyr3]octreotate analogues using click chemistry
  作者：Lisa Iddon、Julius Leyton、Bård Indrevoll、Matthias Glaser、Edward G. Robins、Andrew J.T. George、Alan Cuthbertson、Sajinder Kaur Luthra、Eric O. Aboagye

  DOI：10.1016/j.bmcl.2011.03.016

  日期：2011.5

  A novel class of alkyne linked [Tyr(3)]octreotate analogues have been labelled by a copper catalysed azide-alkyne cycloaddition reaction (CuAAC) to form a 1,4-substituted triazole using the reagent [F-18]2-fluoroethyl azide. An unexpected variability in reactivity during the CuAAC reaction was observed for each alkyne analogue which has been investigated. Two lead alkyne linked [Tyr(3)]octreotate analogues, G-TOCA (3a) and beta AG-TOCA (5a) have been identified to be highly reactive in the click reaction showing complete conversion to the [F-18]2-fluoroethyl triazole linked [Tyr(3)]octreotate analogues FET-G-TOCA (3b) and FET-beta AG-TOCA (5b) under mild conditions and with short synthesis times (5 min at 20 degrees C). As well as ease of synthesis, in vitro binding to the pancreatic tumour AR42J cells showed that both FET-G-TOCA and FET-beta AG-TOCA have high affinity for the somatostatin receptor with IC50 of 4.0 +/- 1.4, and 1.6 +/- 0.2 nM, respectively. (C) 2011 Elsevier Ltd. All rights reserved.