【作者】 江林；

【导师】 李铁津； 杨文胜；

【作者基本信息】 吉林大学 ， 物理化学， 2005， 博士

【摘要】 硫代DNA 作为反义DNA 中的重要一族,被用于各种体内和体外模型作为DNA 的钝化物,现在已经用于抗病毒感染、癌症治疗、爱滋病治疗等。硫代修饰DNA 是磷酸基团上的非桥联O 原子被S 原子所替代,能够与一些原子在该位上形成化学键,如Cd、Au,也使硫代DNA 分子成为了构建具有特殊结构和功能的纳米结构理想材料。本文通过对硫代修饰寡核苷酸与纳米晶的界面相互作用的研究,并尝试使用这种修饰方式DNA 的特性,为诱导纳米晶组装新的纳米结构提供新的途径和思路。研究了侧链硫代修饰寡聚DNA 与Cd2+离子及利用其诱导合成的CdS纳米晶的作用位点。硫代DNA 在Cd2+离子作用下破坏了PS-oligoG10之间的G碱基氢键配对,并通过Cd2+离与硫代DNA上的磷酸根发生配位作用,硫代DNA 被诱导形成特殊的直径为2 nm 左右的纳米球;当加入S 离子后,利用硫代DNA 诱导合成直径为5 nm 的CdS 纳米晶,但作用位点却由原来的磷酸根位转移到DNA 的碱基位上。研究了硫代修饰寡聚DNA 与表面富Cd2+、富S2-和中性的CdS 纳米晶的界面协同相互作用过程。发现修饰过的寡聚DNA 与表面中性的CdS纳米晶作用表现为正协同作用,与表面富S2-的CdS 纳米晶作用时表现为负协同作用,而与表面富Cd2+的CdS 纳米晶作用则没有协同作用发生。未修饰的寡聚DNA 与表面中性的CdS 纳米晶作用也表现为正协同作用,但其协同作用要小于修饰过的寡聚DNA。研究了硫代侧链修饰寡聚DNA 与Au 纳米晶的界面相互作用,发现这种侧链修饰的DNA 分子在纳米晶表面上的取向为平行取向。而侧链修饰DNA 的平行取向,可以通过影响纳米晶表面所能吸附的DNA 的数量进而控制纳米晶在组装体中的排列方式。我们利用4 种不同长度的侧链修饰的DNA 分子,分别得到了密堆积六方、四方、三方以及线形的四种不同的纳米结构图形。更多还原

【Abstract】 Most important biomolecules, such as DNA, protein etc, their size are 2 to 200 nm similar to nanoparticles. Beacause of the special structure and fundamental features, biomolecules display the several surface and interface properties. Biomolecules are important future building blocks for the formation of nanoparticle architectures of predesigned shapes, sizes and compositions. Nanoparticle have highly interesting optical, electronic, and magnetic properties due to quantum confine effects and surface effects. The using of nanoparticles as biotechnological tool are particularly attractive. one of such application is using fluorescent semiconductor as labels for biological tagging experiments. DNA, as one of most important biomolecules, is particularly suitable to serve as a construction material in nanosciences. The most-studied of the antisense oligodeoxynucleotides are the phosphorothioate analogs (PS oligo-DNA), and there have been many reports in which PS oligo-DNA were used to inhibit over-expression of cellular gene product implicated in cancer and inflammation, HIV-1 replication in HIV-1 infected cells and viral replication. For PS oligo-DNA, the sulfur atom introduced on the phosphate backbone dominates the interaction between the DNA and the nanocrystal. My dissertation is focused on studying the interactions at interfaces of the PS oligo-DNA and nanocrystal. It is attempted to supply a new way to nano-assembly by PS oligo-DNA. There are mainly there parts in this dissertations: 1) The coordination sites of phosphorothioate oligoG10 (PS-oligoG10) with Cd2+ and CdS nanocrystal are studied. It is found that after coordinated with phosphate group of the DNA, Cd2+ ions can destroy the guanine-guanine hydrogen bond of quardruplex assembly of PS-oligoG10 and induce the bending of PS-oligoG10 through coordination of Cd2+ with its phosphate groups. The bended PS-oligoG10/Cd2+ complex is observed as nanosphere with diameter of about 2 nm as shown by TEM. After addition of sodium sulfide, TEM image shows CdS nanocrystals with diameter of about 5 nm was obtained. As a result, the coordination between Cd2+ and PO2-group of the DNA is cleaved and the coordination site of the DNA with CdS nanocrystal is identified to transfer to guanine residue of the DNA. 2) Protein-sized surface Cd2+-rich, S2--rich and neutral CdS nanocrystals were employed as “inorganic proteins”to study the interface binding of更多还原