2-(3-(5-(N-(4-bromobenzyl)acetamido)-1-carboxypentyl)ureido)pentane-1,5-dioic acid

• 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: 2-(3-(5-(N-(4-bromobenzyl)acetamido)-1-carboxypentyl)ureido)pentane-1,5-dioic acid
• 英文别名: N-({(1s)-5-[acetyl(4-Bromobenzyl)amino]-1-Carboxypentyl}carbamoyl)-L-Glutamic Acid；(2S)-2-[[(1S)-5-[acetyl-[(4-bromophenyl)methyl]amino]-1-carboxypentyl]carbamoylamino]pentanedioic acid
• 化学式: C₂₁H₂₈BrN₃O₈
• 分子量: 530.373
• InChiKey: ARLQMQGVVFXZCW-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  173
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(3-(5-(N-(4-bromobenzyl)acetamido)-1-carboxypentyl)ureido)pentane-1,5-dioic acid 、 N-(47-amino-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45-pentadecaoxaheptatetracontyl)-4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzamide 以 甲醇 为溶剂， 生成 C₆₂H₉₉BrF₃N₅O₂₄
  参考文献：
  名称：

  使用随机光修饰的探针鉴定生物活性小分子的蛋白质靶标

  摘要：

  鉴定具有生物活性的小分子的蛋白质靶标通常需要复杂而漫长的亲和探针开发。我们提出了一种用光活化苯基二氮杂胺连接基随机修饰感兴趣的小分子的方法。将所得的异构体混合物缀合至装饰有生物素和荧光团的亲水性共聚物。我们使用几种医学上相关的酶的已知抑制剂验证了这种方法。至少一部分随机衍生物保留了它们与靶标的结合，从而使靶标可视化，分离和鉴定。此外，可以将随机探针的混合物分成多个部分并测试结合亲和力。可以确定活性探针的结构，并重新合成探针以提高结合效率。

  DOI：

  10.1021/acschembio.8b00791
• 作为产物：
  描述：

  (S)-di-tert-butyl 2-(3-((S)-6-amino-1-(tert-butoxy)-1-oxohexan-2-yl)ureido)pentanedioate 在 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.25h， 生成 2-(3-(5-(N-(4-bromobenzyl)acetamido)-1-carboxypentyl)ureido)pentane-1,5-dioic acid
  参考文献：
  名称：

  Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery

  摘要：

  Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), is an established prostate cancer marker and is considered a promising target for specific anticancer drug delivery. Low-molecular-weight inhibitors of GCPII are advantageous specific ligands for this purpose. However, they must be modified with a linker to enable connection of the ligand with an imaging molecule, anticancer drug, and/or nanocarrier. Here, we describe a structure-activity relationship (SAR) study of GCPII inhibitors with linkers suitable for imaging and drug delivery. Structure-assisted inhibitor design and targeting of a specific GCPII exosite resulted in a 7-fold improvement in Ki value compared to the parent structure. X-ray structural analysis of the inhibitor series led to the identification of several inhibitor binding modes. We also optimized the length of the inhibitor linker for effective attachment to a biotin-binding molecule and showed that the optimized inhibitor could be used to target nanoparticles to cells expressing GCPII.

  DOI：

  10.1016/j.bmc.2014.05.061

文献信息

• Rational design of urea-based glutamate carboxypeptidase II (GCPII) inhibitors as versatile tools for specific drug targeting and delivery
  作者：Jan Tykvart、Jiří Schimer、Jitka Bařinková、Petr Pachl、Lenka Poštová-Slavětínská、Pavel Majer、Jan Konvalinka、Pavel Šácha

  DOI：10.1016/j.bmc.2014.05.061

  日期：2014.8

  Glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), is an established prostate cancer marker and is considered a promising target for specific anticancer drug delivery. Low-molecular-weight inhibitors of GCPII are advantageous specific ligands for this purpose. However, they must be modified with a linker to enable connection of the ligand with an imaging molecule, anticancer drug, and/or nanocarrier. Here, we describe a structure-activity relationship (SAR) study of GCPII inhibitors with linkers suitable for imaging and drug delivery. Structure-assisted inhibitor design and targeting of a specific GCPII exosite resulted in a 7-fold improvement in Ki value compared to the parent structure. X-ray structural analysis of the inhibitor series led to the identification of several inhibitor binding modes. We also optimized the length of the inhibitor linker for effective attachment to a biotin-binding molecule and showed that the optimized inhibitor could be used to target nanoparticles to cells expressing GCPII.
• Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes
  作者：Petr Šimon、Tomáš Knedlík、Kristýna Blažková、Petra Dvořáková、Anna Březinová、Libor Kostka、Vladimír Šubr、Jan Konvalinka、Pavel Šácha

  DOI：10.1021/acschembio.8b00791

  日期：2018.12.21

  isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach can thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized

  鉴定具有生物活性的小分子的蛋白质靶标通常需要复杂而漫长的亲和探针开发。我们提出了一种用光活化苯基二氮杂胺连接基随机修饰感兴趣的小分子的方法。将所得的异构体混合物缀合至装饰有生物素和荧光团的亲水性共聚物。我们使用几种医学上相关的酶的已知抑制剂验证了这种方法。至少一部分随机衍生物保留了它们与靶标的结合，从而使靶标可视化，分离和鉴定。此外，可以将随机探针的混合物分成多个部分并测试结合亲和力。可以确定活性探针的结构，并重新合成探针以提高结合效率。