| 1086330-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1086330-62-2
• 化学式: C₃₄H₄₈N₁₄O₁₀
• 分子量: 812.843
• InChiKey: YFOHRMRARVUPGM-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  在 10% Pd/C 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、379.22 kPa 条件下， 反应 18.0h， 生成
  参考文献：
  名称：

  Sequence specific and high affinity recognition of 5′-ACGCGT-3′ by rationally designed pyrrole-imidazole H-pin polyamides: Thermodynamic and structural studies

  摘要：

  Imidazole (Im) and Pyrrole (Py)-containing polyamides that can form stacked dimers can be programmed to target specific sequences in the minor groove of DNA and control gene expression. Even though various designs of polyamides have been thoroughly investigated for DNA sequence recognition, the use of H-pin polyamides (covalently cross-linked polyamides) has not received as much attention. Therefore, experiments were designed to systematically investigate the DNA recognition properties of two symmetrical H-pin polyamides composed of PyImPyIm (5) or f-ImPyIm (3e, f = formamido) tethered with an ethylene glycol linker. These compounds were created to recognize the cognate 5 '-ACGCGT-3 ' through an overlapped and staggered binding motif, respectively. Results from DNaseI footprinting, thermal denaturation, circular dichroism, surface plasmon resonance and isothermal titration microcalorimetry studies demonstrated that both H-pin polyamides bound with higher afinity than their respective monomers. The binding afinity of formamido-containing H-pin 3e was more than a hundred times greater than that for the tetraamide H-pin 5, demonstrating the importance of having a formamido group and the staggered motif in enhancing affinity. However, compared to H-pin 3e, tetraamide H-pin 5 demonstrated superior binding preference for the cognate sequence over its non-cognates, ACCGGT and AAATTT. Data from SPR experiments yielded binding constants of 1.6 x 10(8) M (1) and 2.0 x 10(10) M (1) for PyImPyIm H-pin 5 and f-ImPyIm H-pin 3e, respectively. Both H-pins bound with significantly higher affinity (ca. 100-fold) than their corresponding unlinked PyImPyIm 4 and f-ImPyIm 2 counterparts. ITC analyses revealed modest enthalpies of reactions at 298 K (Delta H of -3.3 and -1.0 kcal mol (1) for 5 and 3e, respectively), indicating these were entropic-driven interactions. The heat capacities (Delta C(p)) were determined to be -116 and -499 cal mol (1) K (1), respectively. These results are in general agreement with Delta C(p) values determined from changes in the solvent accessible surface areas using complexes of the H-pins bound to (5 ' CCACGCGTGG)(2) . According to the models, the H-pins fit snugly in the minor groove and the linker comfortably holds both polyamide portions in place, with the oxygen atoms pointing into the solvent. In summary, the H-pin polyamide provides an important molecular design motif for the discovery of future generations of programmable small molecules capable of binding to target DNA sequences with high affinity and selectivity. 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.034