H-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 | 157610-37-2

• 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: H-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2
• 英文别名: (2S)-N-[(2S)-1-amino-1-oxohexan-2-yl]-1-[(2R)-1-[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide
• CAS: 157610-37-2
• 化学式: C₄₂H₅₇N₉O₇
• 分子量: 799.971
• InChiKey: AIYJYDXTFMRUEV-AQMZNLPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  242
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  异硫氰酸荧光素酯 、 H-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 在 硼酸三钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以66%的产率得到Flu-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH₂
  参考文献：
  名称：

  Synthesis and Characterization of Selective Fluorescent Ligands for the neurokinin NK2 Receptor

  摘要：

  Several fluorescent probes for the NK2 receptor were designed, synthesized, and pharmacologically characterized. These fluorescent ligands are analogues of the selective NK2 heptapeptide antagonist N-alpha-benzoyl-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1, GR94800). They were obtained by substitution of 2,n-diaminoalkyl amino acid (n = 3-6) for Ala(1) and the subsequent coupling of the fluorophore NBD (7-ntrobenz-2-oxa-1,3-diazol-4-yl) or fluoresceinthiocarbamyl to the N-omega amino group. The fluorescent derivatives retained high binding affinities for the NK2 receptor in transfected CHO cells. In contrast, fluorescent derivatives made by replacing the N-alpha-benzoyl group of 1 by NBD or fluorescein were considerably less active. The effect on ligand potency of varying the length of the spacer arm between the peptide moiety and the fluorescent group was also studied. The most potent fluorescent antagonists were N-alpha-benzoyl-Dab(gamma-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (5B), pK(i) = 8.87 for NK2; N-alpha-benzoyl-Orn(delta-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (4B), pK(i) = 8.84; and N-alpha-benzoyl-Lys(epsilon-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (3B), pK(i) = 8.83. These three compounds were highly selective for NK2 over NK3 and NK1 receptors. We show that these fluorescent ligands are useful tools for the detection of NK2 receptor expression by flow cytometry. Additionally, these fluorescent probes should prove valuable for fluorescence microscopy and study of ligand-receptor interaction by spectrofluorimetry.

  DOI：

  10.1021/jm00039a012
• 作为产物：
  描述：

  Fmoc-L-脯氨酸 、 Fmoc-L-苯丙氨酸 、 Fmoc-D-脯氨酸 、 N-alpha-芴甲氧羰基-N-in-叔丁氧羰基-D-色氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 Fmoc-4-methoxy-4'-<(γ-carboxypropyl)oxy>benzhydrylamine alanyl aminomethyl polystyrene 作用下， 生成 H-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2
  参考文献：
  名称：

  Synthesis and Characterization of Selective Fluorescent Ligands for the neurokinin NK2 Receptor

  摘要：

  Several fluorescent probes for the NK2 receptor were designed, synthesized, and pharmacologically characterized. These fluorescent ligands are analogues of the selective NK2 heptapeptide antagonist N-alpha-benzoyl-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1, GR94800). They were obtained by substitution of 2,n-diaminoalkyl amino acid (n = 3-6) for Ala(1) and the subsequent coupling of the fluorophore NBD (7-ntrobenz-2-oxa-1,3-diazol-4-yl) or fluoresceinthiocarbamyl to the N-omega amino group. The fluorescent derivatives retained high binding affinities for the NK2 receptor in transfected CHO cells. In contrast, fluorescent derivatives made by replacing the N-alpha-benzoyl group of 1 by NBD or fluorescein were considerably less active. The effect on ligand potency of varying the length of the spacer arm between the peptide moiety and the fluorescent group was also studied. The most potent fluorescent antagonists were N-alpha-benzoyl-Dab(gamma-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (5B), pK(i) = 8.87 for NK2; N-alpha-benzoyl-Orn(delta-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (4B), pK(i) = 8.84; and N-alpha-benzoyl-Lys(epsilon-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (3B), pK(i) = 8.83. These three compounds were highly selective for NK2 over NK3 and NK1 receptors. We show that these fluorescent ligands are useful tools for the detection of NK2 receptor expression by flow cytometry. Additionally, these fluorescent probes should prove valuable for fluorescence microscopy and study of ligand-receptor interaction by spectrofluorimetry.

  DOI：

  10.1021/jm00039a012

文献信息

• Synthesis and Characterization of Selective Fluorescent Ligands for the neurokinin NK2 Receptor
  作者：Charles G. Bradshaw、Karin Ceszkowski、Gerardo Turcatti、Isabel J. M. Beresford、Andre Chollet

  DOI：10.1021/jm00039a012

  日期：1994.6

  Several fluorescent probes for the NK2 receptor were designed, synthesized, and pharmacologically characterized. These fluorescent ligands are analogues of the selective NK2 heptapeptide antagonist N-alpha-benzoyl-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (1, GR94800). They were obtained by substitution of 2,n-diaminoalkyl amino acid (n = 3-6) for Ala(1) and the subsequent coupling of the fluorophore NBD (7-ntrobenz-2-oxa-1,3-diazol-4-yl) or fluoresceinthiocarbamyl to the N-omega amino group. The fluorescent derivatives retained high binding affinities for the NK2 receptor in transfected CHO cells. In contrast, fluorescent derivatives made by replacing the N-alpha-benzoyl group of 1 by NBD or fluorescein were considerably less active. The effect on ligand potency of varying the length of the spacer arm between the peptide moiety and the fluorescent group was also studied. The most potent fluorescent antagonists were N-alpha-benzoyl-Dab(gamma-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (5B), pK(i) = 8.87 for NK2; N-alpha-benzoyl-Orn(delta-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (4B), pK(i) = 8.84; and N-alpha-benzoyl-Lys(epsilon-NBD)-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (3B), pK(i) = 8.83. These three compounds were highly selective for NK2 over NK3 and NK1 receptors. We show that these fluorescent ligands are useful tools for the detection of NK2 receptor expression by flow cytometry. Additionally, these fluorescent probes should prove valuable for fluorescence microscopy and study of ligand-receptor interaction by spectrofluorimetry.