2-现代医药生物技术概论内容资料.pptVIP

现代医药生物技术概论;中心法则之例外;　　非编码RNA（ncRNAs）可以通过多种遗传机理调控DNA的结构、RNA的表达及蛋白质的翻译和功能，进而在细胞、组织或个体水平上影响生物体的正常生长发育。RNA越来越为人们所重视，一个崭新的RNA时代已来临。;Overview of DNA to RNA to Protein;核糖核酸（RNA）;LincRNA调控作用;Part I: 核酶（Ribozyme） Part II: 适配体(Aptamer)和SELEX技术 Part III: 反义核酸（Antisense） Part IV: RNA干扰（RNA interference, RNAi);核酸技术及药物 ;Part I: Ribozymes(核酶);History of enzymatic catalysis;核酶(Ribozyme);Thomas R.Cech;Sidney Altman ;核酶发现的意义：;核酶发现的意义：; 长期以来，人们认为所有的生命形式在冗长的相互依赖的循环中，信息分子和功能分子是分离的。核酸是信息分子，而蛋白质是功能分子。 核酸性酶的发现给人们以启示，即RNA分子不但有复制的功能，含有复制的信息，而且还有催化的功能。因此既是信息分子，又是功能分子。这些新的概念无疑将对生物前化学的研究开辟新的思路。;How many ribozyme ? Why ?;核酶的酶活性反应种类:;One main reaction: Nucleolytic cleavage Transesterification (SN2);The hammerhead ribozyme (plant virus);The hammerhead ribozyme (plant virus);enzyme, substrate, and cleavage site (A-1.1 and C-17);Hairpin ribozyme;The hepatitis delta ribozyme (human virus);General structure of group II introns; Group I II intron ribozyme (rRNA and mt RNA); Group I intron ribozyme (rRNA and mt RNA);Catalytic efficiency, condition;核糖体是一个核酶;Ribozyme technology;Reference:;Part II: SELEX;适配分子(aptamer) SELEX(指数级富集的配体系统进化技术): Systematic Evolution of Ligands by EXponential enrichment;In vitro selection of RNA molecules that bind specific ligands Andrew D.?Ellington??Jack W.?Szostak Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules. Roughly one in 1010 random sequence RNA molecules folds in such a way as to create a specific binding site for small ligands. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase.Tuerk C, Gold L.High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonal