4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid [2-(3-dimethylamino-propylcarbamoyl)-ethyl]-amide | 210298-54-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid [2-(3-dimethylamino-propylcarbamoyl)-ethyl]-amide
• CAS: 210298-54-7
• 化学式: C₁₄H₂₅N₅O₂
• 分子量: 295.385
• InChiKey: GPXOSEVIYXUSBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  21.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  92.39
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N,N-二甲基-1,3-二氨基丙烷 、 1-Methyl-1H-imidazole-2-carboxylic acid benzotriazol-1-yl ester 、 4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid [2-(3-dimethylamino-propylcarbamoyl)-ethyl]-amide 、 、 alkaline earth salt of/the/ methylsulfuric acid 生成 N-[5-[[5-[[5-[[5-[[3-[3-(dimethylamino)propylamino]-3-oxopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-[4-[2-[[5-[[5-[[3-[3-(dimethylamino)propylamino]-3-oxopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-4-[[1-methyl-4-[(1-methylimidazole-2-carbonyl)amino]pyrrole-2-carbonyl]amino]pyrrol-1-yl]butyl]pyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-1-methylimidazole-2-carboxamide
  参考文献：
  名称：

  A Comparison of H-Pin and Hairpin Polyamide Motifs for the Recognition of the Minor Groove of DNA

  摘要：

  In order to compare strategies for covalent linkage of pyrrole-imidazole (Py-Im) polyamide subunits, equilibrium association constants (K-a) were determined for a series of polyamides coupled either C-N with a gamma-aminobutyric acid linker (hairpin motif) or linked across a central Py/Py pair through a tetramethylene spacer (H-pin motif). Compared to the well-characterized hairpin motif, the H-pin motif represents a unique and relatively unexplored approach for increasing the affinity and the specificity of 2:1 polyamide-DNA complexes. Three H-pin polyamides containing six or 10 aromatic amino acid residues were synthesized by solid-phase methods using a Boc-protected bispyrrole monomer combined with bi-directional synthesis. The DNA-binding properties of six-ring and 10-ring H-pin polyamides were analyzed by quantitative DNase I footprint titration on a DNA fragment containing five or seven base pair match and mismatch sequences, respectively. The homodimeric H-Pin (ImPyPy-beta-Dp)(2)C-4 (site of the tetramethylene linker indicated in bold type) binds to the seven base pair match sequence 5'-TGTCA-3' with K-a = 9.3 x 10(6) M-1 and 9.4-fold specificity relative to the single base mismatch sequence 5'-TGT (T) under bar A-3' (K-a = 9.9 x 10(6) M-1). The heterodimeric H-Pin (ImPyPy-beta-Dp)C-4(AcPyPyPy-beta-Dp) binds a 5'-TGTTA-3' match sequence with K-a = 2.0 x 10(6) M-1 and 3.5-fold specificity versus the single base mismatch sequence 5'-TGT (C) under bar A-3' (K-a = 5.7 x 10(5) M-1). The 10-ring H-pin (ImPyPyPyPy-beta-Dp)(2)C-4 binds to the seven base pair match sequence 5'-TGTAACA-3' with K-a = 4.4 x 10(8) M-1 and 28-fold specificity versus the single base pair mismatch sequence 5'-TG (G) under bar AACA-3' (K-a = 1.6 x 10(7) M-1). We find that H-pin polyamides bind with four- to 180-fold enhanced affinity and two- to 10-fold enhanced specificity relative to unlinked analogues, but with 25- to 150-fold reduced affinity and approximately one- to 20-fold reduced specificity compared to the corresponding hairpin polyamides. These results indicate that H-pin polyamides represent a viable motif for the recognition of predetermined sequences in the DNA minor groove; however, DNA-binding properties appear inferior to the corresponding hairpins.

  DOI：

  10.1002/(sici)1521-3765(19980515)4:5<796::aid-chem796>3.0.co;2-g
• 作为产物：
  描述：

  {5-[2-(3-Dimethylamino-propylcarbamoyl)-ethylcarbamoyl]-1-methyl-1H-pyrrol-3-yl}-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 反应 0.5h， 生成 4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid [2-(3-dimethylamino-propylcarbamoyl)-ethyl]-amide
  参考文献：
  名称：

  A Comparison of H-Pin and Hairpin Polyamide Motifs for the Recognition of the Minor Groove of DNA

  摘要：

  In order to compare strategies for covalent linkage of pyrrole-imidazole (Py-Im) polyamide subunits, equilibrium association constants (K-a) were determined for a series of polyamides coupled either C-N with a gamma-aminobutyric acid linker (hairpin motif) or linked across a central Py/Py pair through a tetramethylene spacer (H-pin motif). Compared to the well-characterized hairpin motif, the H-pin motif represents a unique and relatively unexplored approach for increasing the affinity and the specificity of 2:1 polyamide-DNA complexes. Three H-pin polyamides containing six or 10 aromatic amino acid residues were synthesized by solid-phase methods using a Boc-protected bispyrrole monomer combined with bi-directional synthesis. The DNA-binding properties of six-ring and 10-ring H-pin polyamides were analyzed by quantitative DNase I footprint titration on a DNA fragment containing five or seven base pair match and mismatch sequences, respectively. The homodimeric H-Pin (ImPyPy-beta-Dp)(2)C-4 (site of the tetramethylene linker indicated in bold type) binds to the seven base pair match sequence 5'-TGTCA-3' with K-a = 9.3 x 10(6) M-1 and 9.4-fold specificity relative to the single base mismatch sequence 5'-TGT (T) under bar A-3' (K-a = 9.9 x 10(6) M-1). The heterodimeric H-Pin (ImPyPy-beta-Dp)C-4(AcPyPyPy-beta-Dp) binds a 5'-TGTTA-3' match sequence with K-a = 2.0 x 10(6) M-1 and 3.5-fold specificity versus the single base mismatch sequence 5'-TGT (C) under bar A-3' (K-a = 5.7 x 10(5) M-1). The 10-ring H-pin (ImPyPyPyPy-beta-Dp)(2)C-4 binds to the seven base pair match sequence 5'-TGTAACA-3' with K-a = 4.4 x 10(8) M-1 and 28-fold specificity versus the single base pair mismatch sequence 5'-TG (G) under bar AACA-3' (K-a = 1.6 x 10(7) M-1). We find that H-pin polyamides bind with four- to 180-fold enhanced affinity and two- to 10-fold enhanced specificity relative to unlinked analogues, but with 25- to 150-fold reduced affinity and approximately one- to 20-fold reduced specificity compared to the corresponding hairpin polyamides. These results indicate that H-pin polyamides represent a viable motif for the recognition of predetermined sequences in the DNA minor groove; however, DNA-binding properties appear inferior to the corresponding hairpins.

  DOI：

  10.1002/(sici)1521-3765(19980515)4:5<796::aid-chem796>3.0.co;2-g