trans-cyclopropane-1,2-dicarboxamido{3-[1-methyl-4-(4-amino-1-methylpyrrole-2-carboxamido)pyrrole-2-carboxamido]dimethylaminopropane}

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-cyclopropane-1,2-dicarboxamido{3-[1-methyl-4-(4-amino-1-methylpyrrole-2-carboxamido)pyrrole-2-carboxamido]dimethylaminopropane}
• 英文别名: (1R,2R)-1-N,2-N-bis[5-[[5-[3-(dimethylamino)propylcarbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]cyclopropane-1,2-dicarboxamide
• 化学式: C₃₉H₅₄N₁₂O₆
• 分子量: 786.935
• InChiKey: NFFWDJNFFLCXBB-FQLXRVMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  57
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  201
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  反-1,2-环丙烷二羧酸二甲酯 在 N-甲基吗啉 、 sodium hydroxide 、 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 trans-cyclopropane-1,2-dicarboxamido{3-[1-methyl-4-(4-amino-1-methylpyrrole-2-carboxamido)pyrrole-2-carboxamido]dimethylaminopropane}
  参考文献：
  名称：

  一些头对头连接的DNA小沟结合剂的合成

  摘要：

  已经制备了一系列首尾相连的杂环氨基酸二聚体，用于研究与DNA小沟结合的亲和力和选择性。合成目标的选择由基于计算机的设计主导。已经包括几种新颖的二羧酸连接基，包括吲哚，菲，芴酮和双苯并噻吩。通过印迹分析与DNA的结合表明对衍生自2,7-二氢菲二羧酸的化合物具有很高的亲和力，并且对包含至少4个AT对的AT富集区域具有主要选择性，但具有跨越两个CG碱基对的能力。

  DOI：

  10.1016/s0040-4020(00)00432-4

文献信息

• Isohelicity and Strand Selectivity in the Minor Groove Binding of Chiral (1R,2R)- and (1S,2S)-Bis(netropsin)-1,2-cyclopropanedicarboxamide Ligands to Duplex DNA
  作者：Malvinder P. Singh、Bertrand Plouvier、G. Craig Hill、Juergen Gueck、Richard T. Pon、J. William Lown

  DOI：10.1021/ja00095a002

  日期：1994.8

  The sequence-selective DNA binding within the minor groove of four base pairs long AT rich segments for the naturally occurring oligopyrrolecarboxamides, netropsin and distamycin, have been characterized by NMR and X-ray techniques which provide valuable information on the factors for specific molecular recognition and binding efficiency. A special interest in developing longer dimeric bis-netropsin and bis-distamycin compounds arises from their potential applications as gene control agents targeted against larger DNA segments in a sequence specific manner. Herein we describe the use of fixed C-2-symmetric dimeric arrangements of netropsin segments, in opposing orientations and joined through optically pure cyclopropane-1,2-dicarboxamide templates, to ''extend the code'' for isohelical and chiral recognition of eight AT base pairs long minor groove in a right-handed B-DNA fragment. The structural analysis of the diastereomeric complex formed between d(CGAAAATTTTCG)(2) and (-)-(1R,2R)-bis(netropsin)-1,2-cyclopropanedicarboxamide (BNC), and of that between the same DNA fragment and the enantiomeric (+)-(1S,2S)-BNC ligand, was performed by one- and two-dimensional NMR methods. These results indicate a perfectly matching isohelical and strand specific binding for (1R,2R)-BNC where each of the two netropsin subunits is oriented against a 5'-TTTT site. The cyclopropane linker and the N-methylpyrrole rings follow the natural right-handed twist of the base pairs along the minor groove of the 5'-AAAATTTT segment, and the complex is stabilized by single linear hydrogen bonds with the thymidine O2 atoms, instead of the three-center bifurcated bonds proposed for the binding of netropsin to alternating AT segments. The relative orientation of the cyclopropane group (with its methylene projected away from the DNA) for the (1S,2S)-BNC enantiomer is the same as observed for (1R,2R)-BNC which forces each netropsin subunit to be aligned differently in a less favorable arrangement (against 5'-AAAA sites). Binding in this case therefore induces a further twist of the planar amide groups and two N-methylpyrrole ring systems in each of the netropsin subunits. The twisting is detected by NOE interactions and, in contrast with the situation for (1R,2R)-BNC, is attributed to the adjustments that are required by the inherent affinity for hydrogen-bonding by the amide NHs of (1S,2S)-BNC to the contiguous arrangement of thymidine O2 atoms on the complementary strand.