[(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-2-[6-[(4-iodobenzoyl)amino]hexanoylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid | 1440790-03-3

• 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: [(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-2-[6-[(4-iodobenzoyl)amino]hexanoylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid
• CAS: 1440790-03-3
• 化学式: C₄₀H₅₈BBrIN₇O₁₀
• 分子量: 1014.56
• InChiKey: OOHCWKUADKUPKV-PMUGGPHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.88
• 重原子数：
  60
• 可旋转键数：
  29
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  278
• 氢给体数：
  10
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 三乙胺 、 苯硼酸 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 0.5h， 生成 [(1S)-1-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-3-hydroxy-2-[[(2S)-2-[6-[(4-iodobenzoyl)amino]hexanoylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-4-bromobutyl]boronic acid
  参考文献：
  名称：

  Structural Optimization, Biological Evaluation, and Application of Peptidomimetic Prostate Specific Antigen Inhibitors

  摘要：

  Prostate-specific antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA's role in prostate cancer progression, we prepared a library of peptidyl boronic acid-based inhibitors. To enhance selectivity for PSA vs other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA K-i of 72 nM and chymotrypsin K-i of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of I-125 labeled peptides showed low levels of uptake into tumors compared to other normal tissues.

  DOI：

  10.1021/jm301718c

文献信息

• Structural Optimization, Biological Evaluation, and Application of Peptidomimetic Prostate Specific Antigen Inhibitors
  作者：Maya B. Kostova、D. Marc Rosen、Ying Chen、Ronnie C. Mease、Samuel R. Denmeade

  DOI：10.1021/jm301718c

  日期：2013.6.13

  Prostate-specific antigen (PSA) is a serine protease produced at high levels by normal and malignant prostate epithelial cells that is used extensively as a biomarker in the clinical management of prostate cancer. To better understand PSA's role in prostate cancer progression, we prepared a library of peptidyl boronic acid-based inhibitors. To enhance selectivity for PSA vs other serine proteases, we modified the P1 site of the inhibitors to incorporate a bromopropylglycine group. This allowed the inhibitors to participate in halogen bond formation with the serine found at the bottom of the specificity pocket. The best of these Ahx-FSQn(boro)Bpg had PSA K-i of 72 nM and chymotrypsin K-i of 580 nM. In vivo studies using PSA-producing xenografts demonstrated that candidate inhibitors had minimal effect on growth but significantly altered serum levels of PSA. Biodistribution of I-125 labeled peptides showed low levels of uptake into tumors compared to other normal tissues.