6-(3-Aminopropyl)-13-[2-(dimethylamino)ethyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone | 1234884-98-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-(3-Aminopropyl)-13-[2-(dimethylamino)ethyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone
• 英文别名: 6-(3-aminopropyl)-13-[2-(dimethylamino)ethyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone
• CAS: 1234884-98-0
• 化学式: C₂₁H₂₂N₄O₄
• 分子量: 394.43
• InChiKey: SVGRJQUBVZUVFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(3-Aminopropyl)-13-[2-(dimethylamino)ethyl]-6,13-diazatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),2,4(16),8,10-pentaene-5,7,12,14-tetrone 、 neomycin thioisocyanate 在 吡啶 、 4-二甲氨基吡啶 作用下， 以86%的产率得到
  参考文献：
  名称：

  Probing the Recognition Surface of a DNA Triplex: Binding Studies with Intercalator−Neomycin Conjugates

  摘要：

  Thermodynamic studies on the interactions between intercalator neomycin conjugates and a DNA polynucleotide triplex [poly(dA)center dot 2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide neomycin (3) and anthraquinone neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA)center dot 2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (Tm3-2) at which poly(dA)center dot 2poly(dT) dissociated into poly(dA)center dot poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator neomycin conjugates (1-4) even at a very low concentration (2 mu M). In contrast to intercalator neomycin conjugates, the increment of Tm3-2 of poly(dA)center dot 2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator neomycin conjugates (1-4) to poly(dA)center dot 2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size (similar to 7-7.5) with poly(dA)center dot 2poly(dT) as compared to neomycin (similar to 6.5). The thermodynamic parameters of these intercalator neomycin conjugates with poly(dA). 2poly(dT) were derived from an integrated van't Hoff equation using the Tm3-2 values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA)center dot 2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M-1] of 2 with poly(dA)center dot 2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA)center dot 2poly(a) was mostly enthalpy-driven and gave negative Delta C-p values. The results described here suggest that the binding affinity of intercalator neomycin conjugates for poly(dA) center dot 2poly(a) increases as a function of the surface area of the intercalator-moiety.

  DOI：

  10.1021/bi100071j

文献信息

• Probing the Recognition Surface of a DNA Triplex: Binding Studies with Intercalator−Neomycin Conjugates
  作者：Liang Xue、Hongjuan Xi、Sunil Kumar、David Gray、Erik Davis、Paris Hamilton、Michael Skriba、Dev P. Arya

  DOI：10.1021/bi100071j

  日期：2010.7.6

  Thermodynamic studies on the interactions between intercalator neomycin conjugates and a DNA polynucleotide triplex [poly(dA)center dot 2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide neomycin (3) and anthraquinone neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA)center dot 2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (Tm3-2) at which poly(dA)center dot 2poly(dT) dissociated into poly(dA)center dot poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator neomycin conjugates (1-4) even at a very low concentration (2 mu M). In contrast to intercalator neomycin conjugates, the increment of Tm3-2 of poly(dA)center dot 2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator neomycin conjugates (1-4) to poly(dA)center dot 2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size (similar to 7-7.5) with poly(dA)center dot 2poly(dT) as compared to neomycin (similar to 6.5). The thermodynamic parameters of these intercalator neomycin conjugates with poly(dA). 2poly(dT) were derived from an integrated van't Hoff equation using the Tm3-2 values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA)center dot 2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M-1] of 2 with poly(dA)center dot 2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA)center dot 2poly(a) was mostly enthalpy-driven and gave negative Delta C-p values. The results described here suggest that the binding affinity of intercalator neomycin conjugates for poly(dA) center dot 2poly(a) increases as a function of the surface area of the intercalator-moiety.