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Novel metal complex oligomer which forms triple helix with DNA

与DNA形成三螺旋的新型金属复合低聚物

基本信息

批准号：
06453046
负责人：
KURODA Reiko
金额：
$ 4.67万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06453046/
关键词：
Triple helix Base sequences Metal complexes Chirality CD spectroscopy 3重らせんビピリジン銅錯体

项目摘要

DNA triple helix formation is a unique and an attractive approach towards the control of gene expression and DNA replication. Triple helices are formed by binding a single stranded DNA to a double helical DNA.This is in contrast to the case of antisense RNA/DNA which requires a single stranded nucleic acid target. Triple helix formation is highly sequence selective, however, it is limited to DNA of homopurine-homopyrimidine sequences. To overcome this limitation, we have investigated novel oligomer compounds which on polymerization form a triple helix with a double stranded DNA of general base sequence.Such oligomeric units can be metal complexes, although formation of a smooth backbone in the DNA groove may be problematic in this case. In this project we have designed a novel nucleotide analogue wihch potentially discriminates one particular DNA base from others and can be incorporated into a single stranded DNA.Prior to synthesis, the sequence recognizing ability of the compound was checked by computer modeling and force field calculations. Synthesis of the compound is underway. Additionally, to understand the binding mode of metal complexes in the DNA grooves, copper complexes with chiral ligands have been studied. Ligand binding to DNA was estimated through intrinsic DNA cleaving ability. A method for obtaining quantitative information on the binding of metalloporphyrins to DNA has also been developed based on induced CD spectroscopy.

DNA三股螺旋的形成是一种独特的和有吸引力的控制基因表达和DNA复制的方法。三股螺旋是由单链DNA与双螺旋DNA结合形成的，这与需要单链核酸靶的反义RNA/DNA的情况相反。三股螺旋的形成具有高度的序列选择性，但仅限于高嘌呤-高嘧啶序列的DNA。为了克服这一局限性，我们研究了新的寡聚体化合物，它们在聚合时与具有一般碱基序列的双链DNA形成三股螺旋，这种寡聚体单元可以是金属配合物，尽管在这种情况下在DNA沟中形成光滑的骨架可能是有问题的。本课题设计了一种新的核苷酸类似物，它能识别DNA中的一个碱基，并能与单链DNA结合，在合成前，通过计算机模拟和力场计算验证了该化合物的序列识别能力。该化合物的合成正在进行中。此外，为了了解金属配合物在DNA凹槽中的结合模式，已经研究了具有手性配体的铜配合物。通过固有的DNA切割能力估计配体与DNA的结合。基于诱导CD光谱，还发展了一种获得金属卟啉与DNA结合的定量信息的方法。