(S)-2-{(S)-2-[((S)-1-{(S)-2-[(S)-2-Acetylamino-3-(4-phosphonooxy-phenyl)-propionylamino]-3-methyl-butyryl}-pyrrolidine-2-carbonyl)-amino]-4-methylsulfanyl-butyrylamino}-4-methyl-pentanoic acid

• 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: (S)-2-{(S)-2-[((S)-1-{(S)-2-[(S)-2-Acetylamino-3-(4-phosphonooxy-phenyl)-propionylamino]-3-methyl-butyryl}-pyrrolidine-2-carbonyl)-amino]-4-methylsulfanyl-butyrylamino}-4-methyl-pentanoic acid
• 英文别名: (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-(4-phosphonooxyphenyl)propanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-methylsulfanylbutanoyl]amino]-4-methylpentanoic acid
• 化学式: C₃₂H₅₀N₅O₁₁PS
• 分子量: 743.816
• InChiKey: DDNQOBKWMRXUIA-IRGGMKSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  50
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  266
• 氢给体数：
  7
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  乙酸酐 、 (S)-2-{(S)-2-[((S)-1-{(S)-2-[(S)-2-Amino-3-(4-phosphonooxy-phenyl)-propionylamino]-3-methyl-butyryl}-pyrrolidine-2-carbonyl)-amino]-4-methylsulfanyl-butyrylamino}-4-methyl-pentanoic acid 以 二氯甲烷 为溶剂， 生成 (S)-2-{(S)-2-[((S)-1-{(S)-2-[(S)-2-Acetylamino-3-(4-phosphonooxy-phenyl)-propionylamino]-3-methyl-butyryl}-pyrrolidine-2-carbonyl)-amino]-4-methylsulfanyl-butyrylamino}-4-methyl-pentanoic acid
  参考文献：
  名称：

  Design of Peptidomimetics That Inhibit the Association of Phosphatidylinositol 3-Kinase with Platelet-Derived Growth Factor-β Receptor and Possess Cellular Activity

  摘要：

  Phosphorylated tyrosine residues of growth factor receptors that associate with intracellular proteins containing src-homology 2 (SH2) domains are integral components in several signal transduction pathways related to proliferative diseases such as cancer, atherosclerosis, and restenosis. In particular, a phosphorylated pentapeptide [pTyr(751)-Val-Pro-Met(754)-Leu (PTyr = phosphotyrosine)] derived from the primary sequence of platelet-derived growth factor-beta (PDGF-beta) receptor blocks the association of the C-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to PDGF-beta receptor with an IC50 of 0.445 +/- 0.047 mu M. Further evaluation of the structure-activity relationships for pTyr(751)-Val-Pro-Met-Leu resulted in the design of smaller peptidomimetics with enhanced affinity including Ac-pTyr-Val-Ala-N(C6H13)(2) (IC50 = 0.076 +/- 0.010 mu M). In addition, the phosphotyrosine residue was replaced with a difluorophosphonate derivative [4-phosphono(difluoromethyl)phenylalanine (CF(2)Pmp)] which has been shown to be stable to cellular phosphatases. The extracellular administration of either CF(2)Pmp-Val-Pro-Met-Leu or Ac-CF(2)Pmp-Val-Pro-Met-NH2 in a whole cell assay resulted in specific inhibition of the PDGF-stimulated association from the C-terminal SH2 domain of the p85 subunit of PI 3-kinase to the PDGF-beta receptor in a dose-dependent manner. These compounds were also effective in inhibiting GLUT4 translocation, c-fos expression, and cell membrane ruffling in single-cell microinjection assay.

  DOI：

  10.1021/jm9802766