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

• 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; 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

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）在我创建能够简单地和序列裂解双链DNA的金属络合物的方法中N，N'-Tri（2-吡啶基甲基）-2-S-（氨基甲基）哌啶= S-P3PIPDA，从S-2-氨基吡啶胺与3层型2-氯甲基吡啶的反应中获得[Cu（s-p3pipda）]（clo_4）_2和[ni（s-p3pipda）]（oh__2）]（clo_4）_2，是根据等效量的cu（clo_4）_2 _2 _6H_2 ・6H_2O或NI（SO_4）_2 lig fifty fifty fifty fify fiftial（so_4）_2 llo（clo_4）_2 lo（clo_4）_2 lo（clo_4）_2 llo（clo_4）_2 [Cu（s-p3pIDA）]^<2+>的甲醇中的S-P3piPDA X射线晶体结构显示了三角双锥体和方形金字塔之间的中间结构，其中相等的位置由两个二烷胺（N2和N3）（N2和N3）和两个pyridine Nitrogine nitrogine（N4）和N1和N4 1和N4 1和N44）和偶像均占据。 （N5）。高氯酸盐离子坐标弱：Cu-O为3.55Å.1-2）我们合成1,8-（N-雄性甲基甲基）-BIS（N'，N'，N'，N'-二吡啶基-R，R-Cyclohexane-1,2-2-2-二胺），1至1至DNA的裂解活性在Sode sod.sod insod insod insod insod insod insod insod insod insod sod insod sod insod。一个新颖的Fe复合物1和抗坏血酸钠系统切割了DNA的富含A-T的区域。铂（II）与小腿胸腺DNA的结合，紫外线和cd光谱与插入相比，与DNA相互作用。