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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顺序选择性地切割双链DNA的金属络合物(如博莱霉素，其是一种抗肿瘤抗生素，其导致5‘-GC-3’或5‘-GT-3’处的DNA单链和双链切割)的方法中，我制备了光学活性的五齿配体N，N，N‘-tri(2-pyridylmethyl)-2-S-(aminomethyl)piperidine=S-P3pida，该五齿配体是从S-2-氨基比啶与3等摩尔的2-氯甲基吡啶反应得到的，研究了S-P3pida铜(II)、镍(II)配合物[Cu(S-P3pida)](ClO_4)_2和[Ni(S-P3pida)(OH_2)](ClO_4)_2，[Cu(S-P3pida)](ClO_4)_2和[Ni(S-P3pida)(OH_2)](ClO_4)_2的X射线晶体结构。由等摩尔量的铜(ClO_4)_2·6H_2O或Ni(SO_4)_2·6H_2O(然后加入LiClO_4)与配体S-P3在甲醇中在Ar气氛下反应得到。2+&gt；是介于三角双锥体和正方形金字塔之间的中间结构，其中平方位置由两个叔胺(N_2和N_3)和两个吡啶氮(N_1和N_4)占据，轴向位置由一个吡啶氮(N_5)占据。1-2)合成了1，8-(N-二苯甲酰甲基)-双(N‘，N’-联吡啶甲基-R，R-环己烷-1，2-二胺)，1，在抗坏血酸钠存在下，评价了1，8-(N-二苯甲酰甲基)-双(N‘，N’-联吡啶-R，R-环己烷-1，2-二胺)，1对Å的切割活性。合成了两个新的双核铂(II)配合物：1，3-和1，4-(benzenedimethanethiolate-S)di(2，2‘，2“-terpyridine)platinum(II)氯化物四水合物(2和3)，研究了铂(II)配合物与小牛胸腺DNA的结合作用。