Creation of Novel Macrocyclic Compounds that Selectively Recognize Nucleobases to Control Gene Expression

创造选择性识别核碱基以控制基因表达的新型大环化合物

• 批准号: 07458144
• 负责人: KIMURA Eiichi
• 金额: $ 4.99万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07458144/
• 关键词: Macrocyclic polyamines; Dinuclear zinc complex; Nucleotide recognition; Terbium complex; Anti-HIV activity; Nerve gas; Detoxification; Zinc fluorophore; ダンシルペンダント; 大環状テトラアミン; 二核錯体; ヌクレオシド; 核酸認識; 亜鉛錯体; X線結晶構造; 蛍光

19951)Several di- and trinuclear macrocyclic polyamine complexes have been synthesized, which recognize specific nucleotides (uridien, Thymidine) in oligomers, and barbital. The jstrong interactions were studied by pH-metric titrations and NMR and UV spectroscopic methods.2)A novel polyamine cryptate was synthesized, whose dizinc complex selectively cleaves phosphomonoesters. Intrinsic zinc prooperties in alkaline phosphatase are disclosed.3)A new macrocyclic polyamine-terbium complex waas synthesized and its crystal structure was determined by X-ray study. This complex selectively recognizes guamine among nucleobases by emitting fluorescence.19961)The newly synthesized bis (Zn^<II>-cyclen) complexes were shown to possess very strong anti-HIV activity in vitro.2)The newly synthesized Zn^<II>-cyclen complexes denature poly A-poly U and poly dA-poly dT at rom temperature. These are the first examples of small molecules that effectively modify DNA double strands.3)A New biomimetic zinc fluorophore, dansyl-pendant cyclen, was synthesized, which has a great potential for analysis of trace zinc in cells.4)A new cyclen attached with a long alkyl chain was synthesized. Its zinc complex is one of the best catalysis to detoxify nerve gases like salin.

19951)已经合成了几种双核和三核大环多胺络合物，其识别寡聚物中的特定核苷酸（尿苷、胸苷）和巴比妥。通过pH滴定、核磁共振和紫外光谱研究了它们之间的强相互作用。2）合成了一种新型的多胺穴状化合物，其双锌配合物选择性地切割磷酸单酯。3）合成了一种新的大环多胺铽配合物，用X射线衍射法测定了它的晶体结构。19961）新合成的双（Zn^<II>-cyclen）配合物在体外显示出非常强的抗HIV活性。2）新合成的Zn^<II>-cyclen配合物在室温下使poly A-poly U和poly dA-poly dT变性。这些都是第一个有效修饰DNA双链的小分子的例子。3）合成了一种新的仿生锌荧光团--丹磺酰基侧基大环草烯，它在细胞中痕量锌的分析中具有很大的潜力。它的锌复合物是一种最好的催化剂来解毒神经气体，如沙林。

项目成果

T.Koike et.al: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of phosphomonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II)" J.Am.Chem.Soc. 118(13). 3091-3099 (1996)

T.Koike 等人：“协同双核锌 (II) 离子的新特性：新双核锌 (II) 选择性识别磷酸单酯及其 P-O 酯键断裂”J.Am.Chem.Soc。

H.Hashimoto et.al: "Hydrolysis of Lipophilic Esters Catalyzed by a Zinc (II) Complex of a Long Alkyl-Pendant Macrocyclic Tetraamine in Micellar Solution" J.Am.Chem.Soc.118(45). 10963-10970 (1996)

H.Hashimoto 等人：“胶束溶液中长烷基侧链大环四胺的锌 (II) 络合物催化亲脂酯的水解”J.Am.Chem.Soc.118(45)。

E.Kimura and M Shionoya: ""Zinc Complexes as Targeting Agents for Nucleic Acids"" in "Metal Ions in Biological Systems" ed.by A.Sigel and H.Sigel, Marcel Dekker, Inc. 33. 29-52 (1996)

E.Kimura 和 M Shionoya：A.Sigel 和 H.Sigel 编辑的“生物系统中的金属离子”中的“锌复合物作为核酸的靶向剂”，Marcel Dekker, Inc. 33. 29-52 (1996)

E.Kimura and T.Koike: ""Intrinsic Properties of Zinc (II) Ion Pertinent to Zinc Enzymes"" in 'Advance in Inorganic Chemistry', Ed.by A.G.Sykes, Academic Press. 44. 229-261 (1996)

E.Kimura 和 T.Koike：“与锌酶相关的锌 (II) 离子的内在特性”，载于《无机化学进展》，A.G.Sykes 编，学术出版社。

T. Koike et. al: "Novel Properties of Cooperative Dinuclear Zinc (II) Ions : The Selective Recognition of Phosphmonoesters and Their P-O Ester Bond Cleavage by a New Dinuclear Zinc (II)" J. Am, Chem. Soc. 118 (13). 3091-3099 (1996)

T.小池等人。