酶抑制行为的压电电化学表征及分析应用

Studies on enzymatic inhibition are of great significance in the fields of biomedicine and environmental monitoring. The mechanisms for the pharmaceutical or toxic effects of many active molecules are directly related to their inhibition to some enzymes present in human body, and thus searching new active compounds based on the enzyme targets is currently one of the most important means for new drug discovery. In addition, developing enzyme electrodes to sensitively determine relevant enzyme substrates and inhibitors is one of the most important topics in the biosensing area. Obviously, innovating and developing methods and materials for real-time monitoring of the enzymatic inhibitive process and dynamic evaluation of the enzymatic specific activity to acquire thermodynamics, dynamics and mechanism information on enzymatic inhibition will be helpful for better understanding enzymatic inhibitive behaviors and largely improving relevant applications. In this application project, we plan to investigate the inhibitive behaviors of acetylcholinesterase and heavy metal-sensitive enzymes by use of piezoelectric electrochemistry and other conventional methods, dynamically acquire enzymatic specific activity data and process information, and synthesize new enzyme-nanocomposites based on the high reactivity of enzymes to enhance biosensing signals for the development of new enzyme electrodes for sensitive determination of enzymatic inhibitors and substrates. The research contents are as follows: (1) Biosynthesis and piezoelectric electrochemistry characterization of some enzyme-nanocomposites; (2) Researches on acetylcholinesterase-based enzyme electrodes for analytical applications; (3) Enzymatic inhibitive analysis of heavy metal ions.

酶抑制研究在生物医药和环境监测等领域具有重要意义。很多活性分子产生药效或毒性的机制与其对体内酶活性的抑制直接相关，故以酶为靶标搜寻新的活性化合物是当今新药创制的重要途径之一。研制酶电极以高敏检测底物和酶抑制剂，是生物传感领域的重要研究内容。显然，创新和发展实时监测酶抑制过程和评估酶比活性的分析方法，获取酶抑制热力学、动力学和机理信息，有助于深入了解酶抑制行为和有力促进相关应用。本项目拟采用压电电化学等方法研究乙酰胆碱酯酶和重金属敏感酶相关的酶抑制行为，动态获取酶比活数据和过程信息，并利用酶的高效反应性合成新型酶-纳米复合物并实现对酶反应信号的增敏，研制高敏检测抑制剂和底物分子的新型酶电极。项目研究内容如下：（1）酶-纳米复合材料的生物合成和压电电化学表征；（2）乙酰胆碱酯酶相关的酶电极研究与分析应用；（3）重金属离子的酶抑制分析。

酶抑制研究在生物医药和环境监测等领域具有重要意义。很多活性分子产生药效或毒性的机制与其对体内酶活性的抑制直接相关，故以酶为靶标搜寻新的活性化合物是当今新药创制的重要途径之一。研制酶电极以高敏检测底物和酶抑制剂，是生物传感领域的重要研究内容。开发新型酶生物传感器运用于高效检测环境污染物成为生物传感领域的研究前沿之一。本项目中，我们通过研发新型酶固定材料和固定方法，有效放大酶反应及酶抑制过程信号，研发了系列高性能酶电极及酶抑制型生物传感器并将其应用于酶反应底物及抑制剂等环境污染物的检测，实现了对系列酶反应底物及酶抑制剂（农药或重金属离子）的高效传感。重点开发研制能够有效检测酚类污染物、阿特拉津等农药、砷、汞、六价铬、三价铬等常见对人体危害极严重的污染物的传感器。同时，我们也采用电化学石英晶体微天平技术和阳极溶出伏安技术在无极砷的电化学行为以及痕量无机砷、铅、镉的检测方面开展了系列研究，首次提出基于原位电生氢化学还原As(III)或As(V)，增加As(0)阴极富集，高敏分析As(III)和/或As(V)。另外，基于生物亲和、金属及其化合物纳米材料标记和信号放大，开展了系列高敏安培生物传感研究工作，实现了几种肿瘤标志物和心肌损伤标志物的高敏或准单分子水平超敏检测。