权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Sequence specific double-strand DNA cleavage by an optical active dinuclear iron complex and application for artificial restriction enzyme

光学活性双核铁复合物对序列特异性双链 DNA 的切割及其人工限制性内切酶的应用

基本信息

批准号：
14572034
负责人：
KUROSAKI Hiromasa
金额：
$ 2.18万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572034/
关键词：
iron complex DNA cleavage optical active electronic spectra CD spectra 過酸化水素酸化反応 ESR CDスペクトル

项目摘要

1-1)In my approach to create metal complexes that are capable of cleaving double-strand DNA simultaneously and sequence-selectively (like bleomycin, which is an antitumor antibiotic which causes single and double strand cleavage of DNA at 5'-GC-3' or 5'-GT-3' sites), I prepared an optical active pentadentate ligand, N,N,N'-tri(2-pyridylmethyl)-2-S-(aminomethyl)piperidine = S-P3pipda obtained from the reaction of S-2-aminopiperidine with 3 equimolar amounts of 2-chloromethylpyridine, and investigated the X-ray crystal structures of copper(II) and nickel(II) complexes of S-P3pipda, [Cu(S-P3pipda)](ClO_4)_2 and [Ni(S-P3pipda)(OH_2)](ClO_4)_2 Complexes, [Cu(S-P3pipda)](ClO_4)_2 and [Ni(S-P3pipda)(OH_2)](ClO_4)_2, were prepared from the reaction of an equimolar amount of Cu(ClO_4)_2・6H_2O or Ni(SO_4)_2・6H_2O (followed by addition of LiClO_4) with the ligand S-P3pipda in methanol under argon.The X-ray crystal structure of [Cu(S-P3pida)]^<2+> shows an intermediate structure between trigonal bipyramid and square pyramid in which equatrial positions are occupied by two tertiary amines (N2 and N3) and two pyridine nitrogens (N1 and N4) and axial position by a pyridine nitrogen (N5). Perchlorate ion coordinates weakly : Cu-O is 3.55 Å.1-2)We synthesized 1,8-(N-anthranylmethyl)-bis(N',N'-dipyridylmethyl-R,R-cyclohexane-1,2-diamine), 1, and cleaving activity of 1 to DNA was evaluated in the presence of sodium ascorbate under air. A novel Fe complex 1 and sodium ascorbate system cleaved A-T rich region of DNA.2)Moreover, I have synthesized two new dinuclear platinum(II) complexes, 1,3-and 1,4-(benzenedimethanethiolate-S)di(2,2',2"-terpyridine)platinum(II) chloride tetrahydrate (2 and 3), were synthesized in order to investigate the binding of platinum(II) complexes with calf thymus DNA, which was examined by UV and CD spectroscopies. Complex 2 interacted strongly with DNA by intercalation compared to 3.

1-1）在我创建能够同时和序列选择性地切割双链DNA的金属络合物的方法中，（像博来霉素，它是一种抗肿瘤抗生素，在5’-GC-3’或5’-GT-3’位点引起DNA的单链和双链切割），我制备了光学活性五齿配体，N，N，N'-tri（2-吡啶甲基）-2-S-（氨甲基）哌啶= S-P3 pipda，由S-2-氨基哌啶与3个等摩尔量的2-氯甲基吡啶反应获得，并研究了S-P3 pipda的铜（II）和镍（II）络合物的X射线晶体结构，[铜（S-P3pipda）]（ClO_4）_2和[Ni（S-P3 pipda）（OH_2）]（ClO_4）_2配合物（S-P3pipda）]（ClO_4）_2和[Ni（S-P3pipda）（OH_2）]（ClO_4）_2，等摩尔的Cu（ClO_4）_2·6H_2O或Ni（SO_4）_2·6H_2O反应制得（然后加入LiClO_4）与配体S-P3 pipda在甲醇中在氩气保护下反应。（S-P3 pida）]^<2+>显示了一种介于三角双锥和正方锥之间的中间结构，其中两个叔胺占据了四分之一的位置（N2和N3）和两个吡啶氮（N1和N4）以及轴向位置由一个吡啶氮（N5）组成。1 -2）我们合成了1，8-（N-蒽基甲基）-双（N ′，N ′-二吡啶基甲基-R，R-环己烷-1，2-二胺），1，并在抗坏血酸钠存在下在空气中评价了1对DNA的切割活性。本文还合成了两个新的双核铂（II）配合物：1，3-和1，4-硫代苯二甲酰二胺合成了氯化（2，2 '，2”-三联吡啶）铂（II）四水合物（2和3），以研究铂（II）配合物与小牛胸腺DNA的结合，用紫外光谱和圆二色光谱对其进行了分析。配合物2与DNA通过嵌入作用相互作用较强。