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具有谷胱甘肽过氧化物酶活力的含碲环糊精衍生物
  • ISSN号:0251-0790
  • 期刊名称:高等学校化学学报
  • 时间:2013.9.9
  • 页码:2146-2151
  • 分类:O627.61[理学—有机化学;理学—化学]
  • 作者机构:[1]吉林大学分子酶学工程教育部重点实验室,长春130012, [2]吉林大学理论化学计算国家重点实验室,长春130023
  • 相关基金:国家自然科学基金(批准号:21002040)和吉林大学科学前沿与交叉学科创新项目(批准号:200903093,2010ME005)资助
  • 相关项目:谷胱甘肽过氧化物酶小分子模拟物的双功能设计与研究
中文摘要:

设计并合成了谷胱甘肽过氧化物酶(GPx)模拟物6A,6A’-二苯胺-6B,6B'-二碲桥联够-环糊精(6-AnTeCD),采用双酶偶联法进行GPx活力测定和酶反应动力学分析,通过噻唑蓝(M1Tr)比色法评价了6-AnTeCD对H2O2诱导心肌细胞氧化损伤的保护作用.结果表明,6-AnTeCD催化谷胱甘肽(GSH)还原过氧化氢(H2O2)的活力高于6-AnSeCD、6,6'-二碲桥联嵋-环糊精(6-TeCD)和Ebselen等GPx模拟物.稳态动力学分析显示,6-AnTeCD的催化机制为乒乓机制.6-AnTeCD分子兼具引入底物结合部位和改造催化部位的双重优点,具有分子量小、毒性低及可有效保护心肌细胞免受氧化损伤的优点.

英文摘要:

Because the natural glutathione peroxidase (GPx) has some shortcomings such as instability, antigenicity and poor availability, scientists have paid much attention to its artificial imitation. In the present study, 6A, 6A'-dianilino-6B, 6B'-ditelluro-bis-β-cyclodextrin (6-AnTeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase(GPx). In this novel GPx model, tellurium replaced se- lenium as active atom, aniline group was incorporated into cyclodextrin in proximity to catalyiic tellurium for increasing the stability of nucleophilic intermediate tellurolate, and fl-cyclodextrin(/~-CD) provided a hydro- phobic environment for binding substrate in its cavity. The GPx activities and the kinetics of the mimics were assessed in classical coupled reductase assay. The antioxidant effect of the 6-AnTeCD was evaluated based on MTF assay. The results showed that 6-AnTeCD exhibits better GPx activity than those of 6-AnSeCD, 6-TeCD and Ebselen in the reduction of H2O2 by glutathione (GSH) served in steady-state kinetics studies. Moreover, the novel As native GPx, a ping-pong mechanism was ob- GPx mimic occupied merits of small molecular weight and low toxicity. Especially, the 6-AnTeCD was found that it could protect cardiac muscle cells from the injury induced by H2O2. These data demonstrated that and 6-AnTeCD has excellent potential in treatment of H2O2 -mediated diseases.

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期刊信息
  • 《高等学校化学学报》
  • 北大核心期刊(2011版)
  • 主管单位:中华人民共和国教育部
  • 主办单位:吉林大学 南开大学
  • 主编:周其凤
  • 地址:吉林大学南胡校区
  • 邮编:130012
  • 邮箱:cjcu@jlu.edu.cn
  • 电话:0431-88499216
  • 国际标准刊号:ISSN:0251-0790
  • 国内统一刊号:ISSN:22-1131/O6
  • 邮发代号:12-40
  • 获奖情况:
  • 首届及第二届国家期刊奖,连续两届“百种中国杰出学术期刊”,中国期刊方阵“双高”期刊
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),荷兰文摘与引文数据库,美国工程索引,美国科学引文索引(扩展库),日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),英国英国皇家化学学会文摘,中国北大核心期刊(2000版)
  • 被引量:50676