表面等离子体共振单核苷酸多态性分型新方法研究

项目名称： 表面等离子体共振单核苷酸多态性分型新方法研究

项目编号： No.20805029

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 高强

作者单位： 陕西师范大学

项目金额： 22万元

中文摘要： 本项目提出并拟建立一种简单灵敏的基于表面等离子体共振（SPR）技术进行单核苷酸多态性(SNPs)分型的新方法。含无碱基位点（AP site）的探针ss-DNA与目标基因杂交形成ds-DNA，该ds-DNA中目标碱基与其面对的AP site形成一个疏水的微腔，固定化的探针小分子嵌入该腔体并识别目标碱基，利用SPR 技术监测识别过程并实现SNPs的分型和定量测定。设计和合成能通过氢键识别碱基的探针小分子；研究探针小分子固定化方法；研究液相和固定化探针小分子与含AP site ds-DNA的相互作用及分子识别过程；测量识别过程的相关热力学和动力学参数；研制SPR-SNPs 新传感器件；建立性能优良的小分子探针SPR-SNPs分型传感新方法；探索探针小分子与含AP site 的ds-DNA识别的规律。该项目将为SNPs基础和应用研究提供器件和分析新方法，促进SPR、SNPs和生物传感器等的研究。

中文关键词： 单核苷酸多态性分型;表面等离子体共振;无碱基位点;探针杂环小分子;氢键

英文摘要： A simple approach for single nucleobase polymorphisms (SNPs) typing based on surface plasmon resonance (SPR) is proposed in this project. The probe ss-DNA containing abasic site (AP site) hybridizes with the target ss-DNA so as to place the AP site opposite from a target nucleobase in resulting ds-DNA, by which hydrophobic microenvironments are provided for the immobilized small molecule to recognize target nucleobases through hydrogen bonding. The recognition can be monitored by SPR. The novel SNPs typing method, therefore, can be developed. The main research in the project involves synthesis of small molecules which can recognize nucleobase through hydrogen bonding, immobilization method of small molecule on SPR sensor chip, interaction and kinetics constants between small molecule and AP site-containing ds-DNA, fabrication of the SPR biosensors for SNPs typing, developing SNPs typing method. The project will provide some new devices and methods for the SNPs typing and promote research of foundation and applications on SPR SNPs typing and biosensors.

英文关键词： single nucleobase polymorphisms; surface plasmon resonance; abasic site; small molecule; hydrogen bonding