DNA甲基转移酶活性分析方法研究及抗癌药物的筛选

Aberrant DNA methylation has an intimate relationship with the generation and development of tumors, and as we know, DNA methylation is catalyzed and maintained by DNA methyltransferase (Dnmt). Therefore, Dnmt could be an important target which has and will play an important role in the area of treatment and prevention of diseases. In this work,we will focuse on investigating fast,simple and sensitive methods to detect activity of Dnmt and screen anti-tumor drugs by optical analysis technology based on specific recognition of exonuclease and the designability of DNA molecular with the optical materials, designing and synthesizing a series of high quality functional nanomaterial and nanostructure interfaces, designing and screening DNA chains which are specific recognized by the target probe and coupling immobilized on the nano interface to improve the sensitivity and anti-jamming capability of detection method to recognize and capture target molecular with high specificity capture and recognition. We will study in-depth the basic mechanism of DNA molecular adsorption, assembly and folding on these optical materials. We will also explore the mechanism of biomolecule interaction at the molecular level. Our research will have an important value for diagnose,treatment and precaution of tumor and screening the anticancer drugs.

DNA异常甲基化与肿瘤的发生和演进关系密切，而DNA甲基化是由DNA甲基转移酶（Dnmt）催化发生并维持的。因此，Dnmt 可能成为一个重要的分子靶标, 在疾病的治疗和预防中发挥重要作用。本课题拟利用核酸外切酶特异性识别作用和DNA分子的可设计性，结合光学特性物质，利用光分析技术研究Dnmt活性快速、简便、灵敏的分析新方法以及抗肿瘤药物筛选的新方法；设计和合成一系列高质量的功能纳米材料和纳米结构界面；设计和筛选可被目标探针特异性识别的DNA链，在纳米界面上偶联固定化，提高检测方法的抗干扰能力和灵敏度，实现目标分子的高特异性捕获与识别；深入研究DNA分子和光学物质之间的吸附、组装和折叠的基本机制，从分子水平上探索生物分子作用机制，对肿瘤的诊治和预防以及抗肿瘤药物的筛选具有重要的价值。

DNA异常甲基化与肿瘤的发生和演进关系密切，而DNA甲基化是由DNA甲基转移酶（Dnmt）催化发生并维持的。因此，Dnmt 可能成为一个重要的分子靶标, 在疾病的治疗和预防中发挥重要作用。本项目合成了一系列高质量的功能纳米材料（金纳米粒子AuNPs、氧化石墨烯GO、羟基氧化钴CoOOH纳米片、磁性纳米粒子Fe3O4、铜簇、量子点CdSe/ZnS）；利用纳米材料的特殊性能，结合酶特异性识别能力和DNA分子的可调控性，研究制备比色传感器、荧光传感器、表面等离子体共振传感器、原子吸收传感器、电化学传感器快速、灵敏分析Dnmt活性；将可被目标探针特异性识别的DNA链在纳米界面上固定，实现目标分子的高特异性捕获与识别，提高检测方法的灵敏度和抗干扰能力。这些方法都可以实现对抗癌药物的筛选，有望在肿瘤的诊治和预防方面进一步应用。本项目也对甲基转移酶和切酶的潜在干扰物抑制剂如亚砷酸离子、Cu2+、医药中间体甲基苯肼类物质、食品甜味剂阿斯巴甜、甜蜜素等对酶活性影响进行了研究。