基于配体调控的核酸相关信号通路研究

项目名称： 基于配体调控的核酸相关信号通路研究

项目编号： No.91213302

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 有机化学

项目作者： 周翔

作者单位： 武汉大学

项目金额： 880万元

中文摘要： 核酸在细胞信号转导过程中起着重要作用，本项目拟针对特殊结构核酸和相关蛋白，通过化学小分子与它们的相互作用来探索和调控细胞相关信号转导过程，揭示生命过程规律，推动生物学和医药行业的发展。将在原有的研究基础上，对G-四链核酸和环核苷酸在细胞信号转导中的作用进行深入研究：1）设计合成能对四链核酸结构具有识别作用的化学小分子，研究它们对四链核酸构像转变的调控和与核酸、相关蛋白间的关系和分子作用机理，建立阻断G-四链核酸与结合蛋白相互作用的抗肿瘤药物设计的新策略。2）利用化学小分子探针和相关技术，研究端粒相关信号转导通路中各重要环节的关键端粒相关蛋白之间的相互作用，发现和鉴定信号转导网络的新组分，揭示以端粒体蛋白为中心的新的信号转导通路和功能调控网络。3）利用化学小分子和RNAi策略从与钙信号释放相关的基因中筛选与与cADPR介导的钙信号调控相关蛋白，并建立药效团模型。

中文关键词： 核酸；配体；信号转导；表观遗传修饰；调控

英文摘要： The nucleic acid plays an important role in the process of cellular signal transduction. For the special structure of nucleic acids and proteins as the targets, this project intend to explore the regulation of cell signal transduction process and reveal the law of life processes by small chemical molecules, which is benefit to the development of the pharmaceutical industry and biological research. Based on the current study, we will carry out in-depth research on the role of the G-quadruplex nucleic acid and cyclic nucleotides in cellular signal transduction: 1) Design and synthesis of the chemical molecules which can specific recognize the four-chain structure of nucleic acid (G-quadruplex), and the regulation of conformational change of the G-quadruplex by small molecules. Also we intend to study the relationship between the related proteins and G-quadruplex and their interactions. At last the establishment of a new strategy of anticancer drug design through the block of the interactions of G-quadruplex and protein by small molecules. 2) The study of the interactions of the key telomere-associated proteins which is located in the telomere-associated signal transduction pathway by chemical small molecular probe and related technologies. Then we can discover and identificate the new components in the signal tran

英文关键词： Nucleic Acids；ligand；cell signaling；epigenetic modification；regulation