Tert-butyl 2-[4-[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]-7-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate | 1295584-82-5

• 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: Tert-butyl 2-[4-[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]-7-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate
• 英文别名: tert-butyl 2-[4-[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]-7-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate
• CAS: 1295584-82-5
• 化学式: C₂₆H₄₃N₅O₇
• 分子量: 537.657
• InChiKey: RPXJDBQXORVURR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Tert-butyl 2-[4-[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]-7-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 24.0h， 以10 mg的产率得到(4-carboxymethyl-7-{[2-(2,5-dioxo-2,5-dihydropyrrol-1-yl)-ethylcarbamoyl]methyl}-[1,4,7]triazonan-1-yl)acetic acid trifluoroacetate
  参考文献：
  名称：

  Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules

  摘要：

  Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of >95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) was 8.2 +/- 0.9% IA/g and the tumor-to-blood ratio was 31 +/- 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:239S) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.

  DOI：

  10.1021/bc100470x
• 作为产物：
  描述：

  NOTA-BIS(叔丁基酯) 、 N-(2-氨基乙基)马来酰亚胺三氟乙酸盐 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以62%的产率得到Tert-butyl 2-[4-[2-[2-(2,5-dioxopyrrol-1-yl)ethylamino]-2-oxoethyl]-7-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7-triazonan-1-yl]acetate
  参考文献：
  名称：

  Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules

  摘要：

  Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of >95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) was 8.2 +/- 0.9% IA/g and the tumor-to-blood ratio was 31 +/- 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:239S) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.

  DOI：

  10.1021/bc100470x

文献信息

• HER2 BINDING PEPTIDES LABELED WITH ALUMINIUM-[18] FLUORIDE COMPLEXED BY NOTA
  申请人：Hiscock Duncan

  公开号：US20130287685A1

  公开（公告）日：2013-10-31

  Imaging agents comprising an isolated polypeptide conjugated with a radionucleide and a chelator; wherein the isolated polypeptide binds specifically to HER 2 , or a variant thereof; and methods for preparing and using these imaging agents.

  成像剂包括一个与放射性核素和螯合剂结合的分离多肽；其中，分离多肽特异地结合于HER2或其变体；以及制备和使用这些成像剂的方法。
• HER2 BINDING PEPTIDES LABELLED WITH A 18F - CONTAINING ORGANOSILICON COMPOUND
  申请人：Hiscock Duncan

  公开号：US20130295010A1

  公开（公告）日：2013-11-07

  Imaging agents comprising an isolated polypeptide conjugated with a radionucleide and a chelator; wherein the isolated polypeptide binds specifically to HER2, or a variant thereof; and methods for preparing and using these imaging agents.

  成像剂包括一个与放射性核素和螯合剂结合的孤立多肽；其中孤立多肽特异性结合HER2或其变异体；以及制备和使用这些成像剂的方法。
• US9061080B2
  申请人：——

  公开号：US9061080B2

  公开（公告）日：2015-06-23
• Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules
  作者：Vladimir Tolmachev、Mohamed Altai、Mattias Sandström、Anna Perols、Amelie Eriksson Karlström、Frederic Boschetti、Anna Orlova

  DOI：10.1021/bc100470x

  日期：2011.5.18

  Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:239S) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:239S) with In-111 gave a yield of >95% after 20 min at 60 degrees C. In vitro cell tests demonstrated specific binding of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) was 8.2 +/- 0.9% IA/g and the tumor-to-blood ratio was 31 +/- 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:239S) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [In-111-MMA-NOTA-Cys(61)]-Z(HER2:239S) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.