| 916747-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 916747-21-2
• 化学式: C₂₀H₂₆N₁₀O₅
• 分子量: 486.49
• InChiKey: JRROUWGBLBYGIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  35.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  174.25
• 氢给体数：
  3.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  在 palladium on activated charcoal benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 216.0h， 生成
  参考文献：
  名称：

  SOLUTION PHASE SYNTHESIS OF IMIDAZOLE- AND PYRROLE-CONTAINING HAIRPIN POLYAMIDES

  摘要：

  DOI：

  10.1515/hc.2007.13.1.17
• 作为产物：
  描述：

  4-amino-N-[2-(dimethylamino)ethyl]-1-methylimidazole-2-carboxamide 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成
  参考文献：
  名称：

  SOLUTION PHASE SYNTHESIS OF IMIDAZOLE- AND PYRROLE-CONTAINING HAIRPIN POLYAMIDES

  摘要：

  DOI：

  10.1515/hc.2007.13.1.17

文献信息

• Modifying the N-terminus of polyamides: PyImPyIm has improved sequence specificity over f-ImPyIm
  作者：Toni Brown、Hilary Mackay、Mark Turlington、Arden Sutterfield、Traci Smith、Alan Sielaff、Laura Westrate、Chrystal Bruce、Jerome Kluza、Caroline O’Hare、Binh Nguyen、W. David Wilson、John A. Hartley、Moses Lee

  DOI：10.1016/j.bmc.2008.03.008

  日期：2008.5

  Seven N-terminus modified derivatives of a previously published minor-groove binding polyamide (f-ImPyIm, 1) were synthesized and the biochemical and biophysical chemistry evaluated. These compounds were synthesized with the aim of attaining a higher level of sequence selectivity over f-ImPyIm (1), a previously published strong minor-groove binder. Two compounds possessing a furan or a benzofuran moiety at the N-terminus showed a footprint of 0.5 mu M at the cognate ACGCGT site (determined by DNase I footprinting); however, the specificity of these compounds was not improved. In contrast, PyImPyIm (4) produced a footprint of 0.5 mu M but showed a superior specificity using the same technique. When evaluated by thermal melting experiments and circular dichroism using ACGCGT and the non-cognate AAATTT sequence, all compounds were shown to bind in the minor-groove of DNA and stabilize the cognate sequence much better than the non-cognate (except for the non-amido-compound that did not bind either sequence, as expected). PyImPyIm (4) was interesting as the Delta T(m) for this compound was only 4 degrees C but the footprint was very selective. No binding was observed for this compound with a third DNA (non-cognate, ACCGGT). ITC studies on compound 4 showed exothermic binding with ACGCGT and no heat change was observed for titrating the compound to the other two DNA sequences. The heat capacity (Delta C(p)) of the PIPI/ACGCGT complex calculated from the hydrophobic interactions and SASA calculations was comparable to the experimental value obtained from ITC (-146 cal mol(-1) K(-1)). SPR results provided con. firmation of the sequence specificity of PyImPyIm (4), with a K(eq) value determined to be 7.1 x 10(6) M(-1) for the cognate sequence and no observable binding to AAATTT and ACCGGT. Molecular dynamic simulations affirmed that PyImPyIm (4) binds as a dimer in an overlapped conformation, and it fits snugly in the minor-groove of the ACGCGT oligonucleotide. PyImPyIm (4) is an especially interesting molecule, because although the binding affinity is slightly reduced, the specificity with respect to f-ImPyIm (1) is significantly improved. (C) 2008 Elsevier Ltd. All rights reserved.