具有清除羟自由基能力的GPX模拟物的研究
发布时间：2018-11-19 13:54
【摘要】： 谷胱甘肽过氧化物酶(GPX)是生物体内重要的抗氧化酶,能有效地清除活性氧自由基,但是此酶来源有限、稳定性差、分子量大等缺点限制了它的药用前景。因此,人们把注意力集中在对它的人工模拟上。我室利用环糊精空腔作为底物结合口袋、二碲桥为催化中心合成出含咪唑的环糊精衍生物6-ImTeCD,用来模拟GPX。实验结果表明该模拟物具有较高的GPX活力,且催化机制、最适pH值和最适温度均与天然酶相似。6-ImTeCD的加入可使罗丹明B分子免受羟自由基的破坏,证明了该模拟酶具有预期的双重抗氧化损伤能力。建立过氧化氢损伤肝细胞的模型,细胞表现出脂质过氧化损伤,且损伤程度与过氧化氢浓度存在剂量依赖性,6-ImTeCD的加入降低了细胞内MDA生成量、提高了损伤细胞存活率、预防了细胞内LDH的泄漏,使细胞膜能够保持良好的通透性,很好地保护了肝细胞,使其免受氧化损伤。另外,6-ImTeCD能够穿过细胞膜进入肝细胞中,使该分子极有可能成为预防和治疗由ROS介导的疾病的药物前体。
[Abstract]:Glutathione peroxidase (GPX) is an important antioxidant enzyme which can effectively scavenge reactive oxygen free radicals. However, its limited sources, poor stability and high molecular weight limit its medicinal prospects. Therefore, attention is focused on the artificial simulation of it. A cyclodextrin derivative 6-ImTeCD-containing imidazolium was synthesized by using cyclodextrin cavity as substrate binding pocket and tellurium bridge as catalytic center in our room, which was used to simulate GPX.. The experimental results show that the mimic has high GPX activity, and its catalytic mechanism, optimum pH value and optimum temperature are similar to those of natural enzymes. The addition of 6-ImTeCD can protect Rhodamine B from the destruction of hydroxyl radical. It is proved that the mimic enzyme has the expected ability of double antioxidant damage. The model of hydrogen peroxide injury of hepatocytes was established. The cells showed lipid peroxidation damage in a dose-dependent manner. The addition of 6-ImTeCD decreased the MDA production and increased the survival rate of the injured cells. It can prevent the leakage of intracellular LDH, keep the membrane permeability and protect hepatocytes from oxidative damage. In addition, 6-ImTeCD can penetrate the cell membrane into the hepatocytes, making the molecule a potential drug precursor for the prevention and treatment of ROS-mediated diseases.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R341
本文编号：2342505
[Abstract]:Glutathione peroxidase (GPX) is an important antioxidant enzyme which can effectively scavenge reactive oxygen free radicals. However, its limited sources, poor stability and high molecular weight limit its medicinal prospects. Therefore, attention is focused on the artificial simulation of it. A cyclodextrin derivative 6-ImTeCD-containing imidazolium was synthesized by using cyclodextrin cavity as substrate binding pocket and tellurium bridge as catalytic center in our room, which was used to simulate GPX.. The experimental results show that the mimic has high GPX activity, and its catalytic mechanism, optimum pH value and optimum temperature are similar to those of natural enzymes. The addition of 6-ImTeCD can protect Rhodamine B from the destruction of hydroxyl radical. It is proved that the mimic enzyme has the expected ability of double antioxidant damage. The model of hydrogen peroxide injury of hepatocytes was established. The cells showed lipid peroxidation damage in a dose-dependent manner. The addition of 6-ImTeCD decreased the MDA production and increased the survival rate of the injured cells. It can prevent the leakage of intracellular LDH, keep the membrane permeability and protect hepatocytes from oxidative damage. In addition, 6-ImTeCD can penetrate the cell membrane into the hepatocytes, making the molecule a potential drug precursor for the prevention and treatment of ROS-mediated diseases.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R341
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相关期刊论文 前1条
1 尤长城,刘育;超分子体系中的分子识别研究(一)——有机硒修饰β-环糊精的合成及其与L-和D-色氨酸的包结配位作用[J];高等学校化学学报;2000年02期
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