6-benzoylamino-2-bromo-hexanoic acid methyl ester | 100721-27-5

• 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: 6-benzoylamino-2-bromo-hexanoic acid methyl ester
• 英文别名: methyl 6-benzamido-2-bromohexanoate；6-Benzoylamino-2-brom-hexansaeure-methylester
• CAS: 100721-27-5
• 化学式: C₁₄H₁₈BrNO₃
• 分子量: 328.206
• InChiKey: ZMEAKSZWRNBPFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  19.0
• 可旋转键数：
  7.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6-benzoylamino-2-bromo-hexanoic acid methyl ester 、 1,4,7-三氮杂环壬烷-1,4-二乙酸二叔丁酯 在 potassium carbonate 、 盐酸 作用下， 以 乙腈 、 水 为溶剂， 生成 1,4,7-triazacyclononane-N,N′,N″-triacetic acid
  参考文献：
  名称：

  Site-Specific Immuno-PET Tracer to Image PD-L1

  摘要：

  The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific alpha PD-L1 Fab conjugate with the chelator 1,4,7-triazacyclononane-N,N',N ''-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), p-azidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, Cu-64-NOTA-alpha PD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.

  DOI：

  10.1021/acs.molpharmaceut.9b00010
• 作为产物：
  描述：

  苯甲酰氯 在 磷化氢 、 溴 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 6-benzoylamino-2-bromo-hexanoic acid methyl ester
  参考文献：
  名称：

  Site-Specific Immuno-PET Tracer to Image PD-L1

  摘要：

  The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific alpha PD-L1 Fab conjugate with the chelator 1,4,7-triazacyclononane-N,N',N ''-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), p-azidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, Cu-64-NOTA-alpha PD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.

  DOI：

  10.1021/acs.molpharmaceut.9b00010

文献信息

• Maimind et al., Zhurnal Obshchei Khimii, 1956, vol. 26, p. 2313,2315; engl. Ausg. S. 2587, 2589
  作者：Maimind et al.

  DOI：——

  日期：——