GPLG | 20989-50-8

• 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: GPLG
• 英文别名: glycyl-L-prolyl-L-leucylglycine
• CAS: 20989-50-8
• 化学式: C₁₅H₂₆N₄O₅
• 分子量: 342.395
• InChiKey: BSXLDWGXHQGZAH-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.33
• 重原子数：
  24.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  141.83
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  Z-Gly-Pro-Leu-Gly 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 0.5h， 生成 GPLG
  参考文献：
  名称：

  Moir, Michael E.; Crawford, Robert J., Canadian Journal of Chemistry, 1988, vol. 66, p. 2903 - 2913

  摘要：

  DOI：

文献信息

• Photodynamic Molecular Beacons Triggered by MMP-2 and MMP-9: Influence of the Distance Between Photosensitizer and Quencher onto Photophysical Properties and Enzymatic Activation
  作者：M. Verhille、H. Benachour、A. Ibrahim、M. Achard、P. Arnoux、M. Barberi-Heyob、J.-C. Andre、X. Allonas、F. Baros、R. Vanderesse、C. Frochot

  DOI：10.2174/092986712803833128

  日期：2012.10.1

  Angiogenesis is a key step in the tumoral progression process. It is characterized by an over-expression of a number of matrix metalloproteinases (MMP). Among these MMPs, gelatinases (MMP-2 and MMP-9) are known to play a critical role in tumor angiogenesis and the growth of many cancers. Photodynamic Molecular Beacons (PMB) can be designed for cancer treatment by associating a chlorin-like photosensitizer and a black hole quencher linked by a gelatinase substrate peptide with the aim of silencing photosensitizer toxicity in non-targeted cells and restore its toxicity only in surrounding gelatinases. This article provides a report on the synthesis and photophysical and biochemical studies of new families of PMB, using tetraphenylchlorin and a black hole quencher as a donor-acceptor pair, and MMP specific sequence (H-Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln-Lys-OH or H-Pro-Leu-Gly-Leu-OH) to keep them in close proximity. Different spacers were used to evaluate the influence of the distance between the photosensitizer and the quencher on the photophysical properties and enzymatic activation of the PMB. Time-resolved quenching experiments were performed and FRET energy transfer could be observed. Photosensitizers’ triplet state band in transient absorption disappears in PMB. However, even if both MMP-2 and MMP-9 were found to efficiently cleave the peptide alone, no cleavage was observed for all PMB. Further studies would be required to assess the ability of the PMB constructs to retain the sensitivity of the peptide linker to be cleaved by matrix metalloproteinases.

  血管生成是肿瘤进展过程中的一个关键步骤。它的特点是多种基质金属蛋白酶（MMP）的过度表达。在这些MMP中，明胶酶（MMP-2和MMP-9）被认为在肿瘤血管生成和多种癌症的生长中起着关键作用。可以通过将类似氯化物的光敏剂与通过明胶酶底物肽连接的黑洞灭活剂结合，设计光动力分子信标（PMB）用于癌症治疗，目的是在非靶细胞中沉默光敏剂的毒性，并仅在周围的明胶酶中恢复其毒性。本文报告了新型PMB家族的合成及其光物理和生化研究，使用四苯基氯化物和黑洞灭活剂作为供体-受体对，并采用MMP特异性序列（H-Gly-Pro-Leu-Gly-Ile-Ala-Gly-Gln-Lys-OH或H-Pro-Leu-Gly-Leu-OH）使它们保持近距离。使用不同的间隔物来评估光敏剂与灭活剂之间距离对PMB的光物理特性和酶活化的影响。进行了时间分辨的猝灭实验，并观察到了FRET能量转移。在PMB中，光敏剂的三重态吸收带在瞬态吸收中消失。然而，尽管发现MMP-2和MMP-9都能有效切割肽链，但在所有PMB中都未观察到切割现象。需要进一步研究以评估PMB构建体保持肽链连接部位被基质金属蛋白酶切割的敏感性的能力。