化学小分子作为DNA序列和结构特异性识别剂的研究

项目名称： 化学小分子作为DNA序列和结构特异性识别剂的研究

项目编号： No.20802055

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 化学工业

项目作者： 翁小成

作者单位： 武汉大学

项目金额： 24万元

中文摘要： 在本基金的资助下，我们开展了DNA序列和结构识别的研究和其它衍生工作，如下：（1）设计合成了一种硒苯基寡聚核苷酸的共聚物，能在氧化诱导下特异性对互补序列产生DNA的交联，若有突变发生则交联消失，达到序列选择性的效果；（2）针对特殊的DNA结构，设计合成了钌多吡啶配合物和锰Corrole化合物，对非双链区域的鸟嘌呤达到特异性识别效果；（3）设计合成了联苯酚季铵盐-寡聚酰胺衍生物和芘-寡聚酰胺衍生物，并对他们的生物活性作了初步研究；（4）通过对DNA过氧化物酶的DNA序列的末端进行突变的策略，利用紫外光谱，圆二色谱等实验手段，较系统地研究了DNA过氧化物酶的结构与酶活力的关系；（5）基于四链核酸结构和石墨烯，发展了一种特异性检测Ag离子的检测体系，继续还可将此体系延伸成为半胱氨酸的检测系统。通过项目资助和三年的研究，发表了多篇SCI论文，获得授权专利1项，培养2名硕士研究生，项目负责人获得2010年湖北省自然科学一等奖（第2完成人），并获得RSC"Young Chemist Award"资助参加了在英国格拉斯哥举行的第42届IUPAC年会。

中文关键词： DNA序列；结构识别；寡聚酰胺；DNA过氧化物酶；Ag+检测

英文摘要： We have done some research works as following in support of this funding. (1) We have designed and synthesized a selenium phenyl-oligonucleotide conjugate. The selenide derivatives can generate covalent interstrand cross-linking with its complementary strand. (2) We focused on the non-duplex regions of DNA and synthesized some manganese(III) corroles and Ruthenium complexes, which exhibited highly selective cleavage ability for guanosine units located at non-duplex portions, such as loops and bulges. (3) The polyamide derivatives with bipheol quaternary ammonium salt or pyrene were designed and synthesized and its biological activities was investigated. (4)We present the preliminary investigation on the relationship between the structure and function of DNAzymes through a terminal oligo modification in a G-quadruplex sequences by adding different lengths of oligo-dT to the 3'- or 5'-end of the aptamers. (5) We developed a sensitive and selective Ag+ and Cys detection system which based on graphene oxide and G-quadruplex DNA. In conclusion, the achievements of this funding contained some SCI publications, one authorized patents, two Master's degree students and the first prize of Natural Science Award of Hubei Province (second). In addition, I have attented the 42nd IUPAC meeting in Glasgow by the financial supports of RSC young chemist award and this funding.

英文关键词： DNA sequence; structural recognition; polyamide; DNAzyme; Ag+ sensor