YSAYPDSVPMMS[Nε-(5-hexynoyl)lysine] | 1246194-71-7

• 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: YSAYPDSVPMMS[Nε-(5-hexynoyl)lysine]
• CAS: 1246194-71-7
• 化学式: C₇₁H₁₀₄N₁₄O₂₂S₂
• 分子量: 1569.82
• InChiKey: QSYOQVKIBGBCOS-DORTVKBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.15
• 重原子数：
  109.0
• 可旋转键数：
  47.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  562.49
• 氢给体数：
  19.0
• 氢受体数：
  23.0

反应信息

• 作为反应物：
  描述：

  2'-[2-(2-(6-azidohexyloxy)-2-oxoethoxy)acetyl]-O-paclitaxel 、 YSAYPDSVPMMS[Nε-(5-hexynoyl)lysine] 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 48.0h， 以65%的产率得到YSAYPDSVPMMS[Nε-(5-hexynoyl)lysine]-PTX
  参考文献：
  名称：

  Novel Targeted System To Deliver Chemotherapeutic Drugs to EphA2-Expressing Cancer Cells

  摘要：

  The efficacy of anticancer drugs is often limited by their systemic toxicities and adverse side effects. We report that the EphA2 receptor is overexpressed preferentially in several human cancer cell lines compared to normal tissues and that an EphA2 targeting peptide (YSAYPDSVPMMS) can be effective in delivering anticancer agents to such tumors. Hence, we report on the synthesis and characterizations of a novel EphA2-targeting agent conjugated with the chemotherapeutic drug paclitaxel. We found that the peptide-drug conjugate is dramatically more effective than paclitaxel alone at inhibiting tumor growth in a prostate cancer xenograft model, delivering significantly higher levels of drug to the tumor site. We believe these studies open the way to the development of a new class of therapeutic compounds that exploit the EphA2 receptor for drug delivery to cancer cells.

  DOI：

  10.1021/jm201743s
• 作为产物：
  描述：

  5-己炔酸 、 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)-6-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]chromen-4-one 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 肼 、 三氟乙酸 、 苯酚 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 3.0h， 以992 mg的产率得到YSAYPDSVPMMS[Nε-(5-hexynoyl)lysine]
  参考文献：
  名称：

  Novel Targeted System To Deliver Chemotherapeutic Drugs to EphA2-Expressing Cancer Cells

  摘要：

  The efficacy of anticancer drugs is often limited by their systemic toxicities and adverse side effects. We report that the EphA2 receptor is overexpressed preferentially in several human cancer cell lines compared to normal tissues and that an EphA2 targeting peptide (YSAYPDSVPMMS) can be effective in delivering anticancer agents to such tumors. Hence, we report on the synthesis and characterizations of a novel EphA2-targeting agent conjugated with the chemotherapeutic drug paclitaxel. We found that the peptide-drug conjugate is dramatically more effective than paclitaxel alone at inhibiting tumor growth in a prostate cancer xenograft model, delivering significantly higher levels of drug to the tumor site. We believe these studies open the way to the development of a new class of therapeutic compounds that exploit the EphA2 receptor for drug delivery to cancer cells.

  DOI：

  10.1021/jm201743s

文献信息

• Design, Synthesis and Bioevaluation of an EphA2 Receptor-Based Targeted Delivery System
  作者：Elisa Barile、Si Wang、Swadesh K. Das、Roberta Noberini、Russell Dahl、John L. Stebbins、Elena B. Pasquale、Paul B. Fisher、Maurizio Pellecchia

  DOI：10.1002/cmdc.201400067

  日期：2014.7

  Because of its overexpression in a range of solid tumors, the EphA2 receptor is a validated target for cancer therapeutics. We recently described a new targeted delivery system based on specific EphA2‐targeting peptides conjugated with the chemotherapeutic agent paclitaxel. Here, we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing

  由于其在一系列实体瘤中的过度表达，EphA2 受体是癌症治疗的有效靶点。我们最近描述了一种新的靶向递送系统，该系统基于与化疗剂紫杉醇结合的特定 EphA2 靶向肽。在这里，我们研究了负责这些试剂在血浆中的稳定性和降解的化学决定因素。在肽和肽与紫杉醇之间的接头中引入修饰导致药物偶联物在大鼠血浆中的寿命很长，并且与单独使用紫杉醇相比，在前列腺癌异种移植模型中显着减小了肿瘤大小。这些研究确定了肽-药物偶联物上的关键限速降解位点，从而能够设计出具有更高稳定性和功效的药物。