VV-Hemorphin-7 | 75808-67-2

• 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: VV-Hemorphin-7
• 英文别名: Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe；VVYPWTQRF；(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoic acid
• CAS: 75808-67-2
• 化学式: C₅₉H₈₂N₁₄O₁₃
• 分子量: 1195.39
• InChiKey: FFBBHLKDMHCFTH-AKYHLAPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  86
• 可旋转键数：
  32
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  451
• 氢给体数：
  15
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  LLVVYPWTQRFF 在 cathepsin D 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 生成 L-亮氨酰-L-亮氨酸 、 LVVYPWTQRFF 、 VVYPWTQRFF 、 LLVVYPWTQRF 、 VV-Hemorphin-7 、 rat LVV-hemorphin-7
  参考文献：
  名称：

  Cathepsin D activity and selectivity in the acidic conditions of a tumor microenvironment: Utilization in the development of a novel Cathepsin D substrate for simultaneous cancer diagnosis and therapy

  摘要：

  Pro-Cathepsin D (pCD) is an aspartyl endopeptidase which is over expressed in many cancers. This over expression generally led to its secretion into the extracellular culture medium of cancer cells. Moreover, pCD can auto activate and cleave its substrates at an acidic pH compatible with that found in tumor microenvironments (TME). Thus, exploiting these two pathological characteristics of TME offers the opportunity to develop new protease-activated vector on the basis of their specific substrate structures. The aim of this study was to validate new pCD substrates in the extracellular pH conditions of TME. As a first step, we investigated the effect of pH on the catalytic activity and selectivity of mature Cathepsin D (CD). It was found that the increase in the pH of the media led to a decrease in the reaction rate. However, the specificity of mature CD was not affected by a variation in pH. In the second step, the effect of the substrate structure was studied. We demonstrated that the substrate structure had a significant effect on the catalytic activity of CD. In fact, some modifications in peptide structure induced a change in the catalytic behavior that involved a substrate activation phenomenon. We suggest that this activation may be related to the amphiphilic nature of the modified peptide that may induce an interfacial activation mechanism. Finally, pCD, which is the major form found in the extracellular culture medium of cancer cells, was used. We demonstrated that the proform of CD cleave the modified peptide 5 at pH 6.5 with the same cleavage selectivity obtained with the mature form of the protease. These data provide a better understanding of CD behavior in tumor microenvironment conditions and this knowledge can be used to develop more specific tools for diagnosis and drug delivery. (C) 2013 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.biochi.2013.07.010

文献信息

• Cathepsin D activity and selectivity in the acidic conditions of a tumor microenvironment: Utilization in the development of a novel Cathepsin D substrate for simultaneous cancer diagnosis and therapy
  作者：Oussama Achour、Nicolas Bridiau、Meriem Kacem、Régis Delatouche、Stéphanie Bordenave-Juchereau、Frédéric Sannier、Valérie Thiéry、Jean-Marie Piot、Thierry Maugard、Ingrid Arnaudin

  DOI：10.1016/j.biochi.2013.07.010

  日期：2013.11

  Pro-Cathepsin D (pCD) is an aspartyl endopeptidase which is over expressed in many cancers. This over expression generally led to its secretion into the extracellular culture medium of cancer cells. Moreover, pCD can auto activate and cleave its substrates at an acidic pH compatible with that found in tumor microenvironments (TME). Thus, exploiting these two pathological characteristics of TME offers the opportunity to develop new protease-activated vector on the basis of their specific substrate structures. The aim of this study was to validate new pCD substrates in the extracellular pH conditions of TME. As a first step, we investigated the effect of pH on the catalytic activity and selectivity of mature Cathepsin D (CD). It was found that the increase in the pH of the media led to a decrease in the reaction rate. However, the specificity of mature CD was not affected by a variation in pH. In the second step, the effect of the substrate structure was studied. We demonstrated that the substrate structure had a significant effect on the catalytic activity of CD. In fact, some modifications in peptide structure induced a change in the catalytic behavior that involved a substrate activation phenomenon. We suggest that this activation may be related to the amphiphilic nature of the modified peptide that may induce an interfacial activation mechanism. Finally, pCD, which is the major form found in the extracellular culture medium of cancer cells, was used. We demonstrated that the proform of CD cleave the modified peptide 5 at pH 6.5 with the same cleavage selectivity obtained with the mature form of the protease. These data provide a better understanding of CD behavior in tumor microenvironment conditions and this knowledge can be used to develop more specific tools for diagnosis and drug delivery. (C) 2013 Published by Elsevier Masson SAS.