N-[1-(3-aminopropyl)-5-[[2-[2-(dimethylamino)ethylcarbamoyl]-1-methylimidazol-4-yl]carbamoyl]pyrrol-3-yl]-4-benzamido-1-methylimidazole-2-carboxamide | 1359164-21-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-[1-(3-aminopropyl)-5-[[2-[2-(dimethylamino)ethylcarbamoyl]-1-methylimidazol-4-yl]carbamoyl]pyrrol-3-yl]-4-benzamido-1-methylimidazole-2-carboxamide
• CAS: 1359164-21-8
• 化学式: C₂₉H₃₇N₁₁O₄
• 分子量: 603.684
• InChiKey: FIQYFRAULMSMIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氨基-1-甲基-1H-咪唑-2-羧酸乙酯 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氨 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.25h， 生成 N-[1-(3-aminopropyl)-5-[[2-[2-(dimethylamino)ethylcarbamoyl]-1-methylimidazol-4-yl]carbamoyl]pyrrol-3-yl]-4-benzamido-1-methylimidazole-2-carboxamide
  参考文献：
  名称：

  Novel diamino imidazole and pyrrole-containing polyamides: Synthesis and DNA binding studies of mono- and diamino-phenyl-ImPy*Im polyamides designed to target 5′-ACGCGT-3′

  摘要：

  Pyrrole- and imidazole-containing polyamides are widely investigated as DNA sequence selective binding agents that have potential use as gene control agents. The key challenges that must be overcome to realize this goal is the development of polyamides with low molar mass so the molecules can readily diffuse into cells and concentrate in the nucleus. In addition, the molecules must have appreciable water solubility, bind DNA sequence specifically, and with high affinity. It is on this basis that the orthogonally positioned diamino/dicationic polyamide Ph-ImPy*Im 5 was designed to target the sequence 5'-ACGCGT-3'. Py* denotes the pyrrole unit that contains a N-substituted aminopropyl pendant group. The DNA binding properties of diamino polyamide 5 were determined using a number of techniques including CD, Delta T(M), DNase I footprinting, SPR and ITC studies. The effects of the second amino moiety in Py* on DNA binding affinity over its monoamino counterpart Ph-ImPylm 3 were assessed by conducting DNA binding studies of 3 in parallel with 5. The results confirmed the minor groove binding and selectivity of both polyamides for the cognate sequence 5'-ACGCGT-3'. The diamino/dicationic polyamide 5 showed enhanced binding affinity and higher solubility in aqueous media over its monoamino/monocationic counterpart Ph-ImPylm 3. The binding constant of 5, determined from SPR studies, was found to be 1.5 x 10(7) M(-1), which is similar to 3 times higher than that for its monoamino analog 3 (4.8 x 10(6) M(-1)). The affinity of 5 is now approaching that of the parent compound f-ImPyIm 1 and its diamino equivalent 4. The advantages of the design of diamino polyamide 5 over 1 and 4 are its sequence specificity and the ease of synthesis compared to the N-terminus pyrrole analog 2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.010

文献信息

• Novel diamino imidazole and pyrrole-containing polyamides: Synthesis and DNA binding studies of mono- and diamino-phenyl-ImPy*Im polyamides designed to target 5′-ACGCGT-3′
  作者：Vijay Satam、Balaji Babu、Sameer Chavda、Mia Savagian、Robert Sjoholm、Samuel Tzou、Yang Liu、Konstantinos Kiakos、Shicai Lin、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1016/j.bmc.2011.12.010

  日期：2012.1

  Pyrrole- and imidazole-containing polyamides are widely investigated as DNA sequence selective binding agents that have potential use as gene control agents. The key challenges that must be overcome to realize this goal is the development of polyamides with low molar mass so the molecules can readily diffuse into cells and concentrate in the nucleus. In addition, the molecules must have appreciable water solubility, bind DNA sequence specifically, and with high affinity. It is on this basis that the orthogonally positioned diamino/dicationic polyamide Ph-ImPy*Im 5 was designed to target the sequence 5'-ACGCGT-3'. Py* denotes the pyrrole unit that contains a N-substituted aminopropyl pendant group. The DNA binding properties of diamino polyamide 5 were determined using a number of techniques including CD, Delta T(M), DNase I footprinting, SPR and ITC studies. The effects of the second amino moiety in Py* on DNA binding affinity over its monoamino counterpart Ph-ImPylm 3 were assessed by conducting DNA binding studies of 3 in parallel with 5. The results confirmed the minor groove binding and selectivity of both polyamides for the cognate sequence 5'-ACGCGT-3'. The diamino/dicationic polyamide 5 showed enhanced binding affinity and higher solubility in aqueous media over its monoamino/monocationic counterpart Ph-ImPylm 3. The binding constant of 5, determined from SPR studies, was found to be 1.5 x 10(7) M(-1), which is similar to 3 times higher than that for its monoamino analog 3 (4.8 x 10(6) M(-1)). The affinity of 5 is now approaching that of the parent compound f-ImPyIm 1 and its diamino equivalent 4. The advantages of the design of diamino polyamide 5 over 1 and 4 are its sequence specificity and the ease of synthesis compared to the N-terminus pyrrole analog 2. (C) 2011 Elsevier Ltd. All rights reserved.