A novel detection system based on amplification and a strongly correlated hydrogen network

基于放大和强相关氢网络的新型检测系统

• 批准号: 13031063
• 负责人: TAKENAKA Shigeori
• 金额: $ 8.26万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13031063/
• 关键词: DNA; tetraplex; potassium ion; sensing; intercalator; tetrakis-acridiny peptide; telomerase; telomere DNA; テロメア; カリウム; FRET; TAMRA; FAM; ナトリウム; Oxytricha; 蛍光; 水素結合; センシング材料; テロメアDNA配列; Guanine quartet構造; カリウムインジケーター; 蛍光共鳴エネルギー移動(FRET)

DNA is regarded as a strongly correlated soft material from a viewpoint of polymer chemistry, as its structure is dictated by many cooperative interactions such as hydrogen bonding, pi-pi stacking of aromatic rings, and electrostatic forces. A new material may be developed successfully using these characteristics of DNA. Alternatively, DNA itself may be utilized aiming at developing a DNA synthesizing technology. So far, we stand in the latter position and have been studying materials containing biochemically useful reagents. Here, we discuss a new reagent by using DNA tetraplex formationwhich is one form of complex structures of DNA. 1)Potassium sensing oligonucleotide, PSO Several metal ions have an important role in living organism. Potassium ion is connected with regulation of other metal ions and some diseases and is attracted in the medical area. So far several reagents were studied in this point, but they have insufficient water-solubility and specificity. In this paper, we firstly succeeded the water-soluble sensing reagent for a potassium ion, which showed the very high specificity for potassium ion over sodium one. 2)Tetrakis-acridiny peptide (TAP) as a potential telomerase inhibitor Some of the cancers are believed to be derived from enhanced activity of telomerase, which catalyzes the extension of telomere DNA termini. Since telomerase cannot bind to a G-quartet structure, compounds which can stabilize such a DNA structure are good candidate for telomerase inhibitor. We tested inhibition ability of TAP, which interacts with DNA, for telomerase. TAP had remarkable stabilization power of a G-quartet structure and hence is promising as a novel telomerase inhibitor.

从高分子化学的角度来看，DNA被认为是一种强相关的软材料，因为它的结构是由许多协同相互作用决定的，例如氢键、芳香环的π-π堆积和静电力。利用 DNA 的这些特性可以成功开发出新材料。或者，可以利用DNA本身来开发DNA合成技术。到目前为止，我们站在后一个立场，一直在研究含有生化有用试剂的材料。在这里，我们讨论一种利用 DNA 四链体形成的新试剂，DNA 四链体形成是 DNA 复杂结构的一种形式。 1)钾传感寡核苷酸，PSO 几种金属离子在生物体中具有重要作用。钾离子与其他金属离子和某些疾病的调节有关，并在医学领域受到关注。迄今为止，在这方面研究了几种试剂，但它们的水溶性和特异性都不够。在本文中，我们首次成功研制出钾离子的水溶性传感试剂，其对钾离子的特异性高于钠离子。 2）四吖啶肽（TAP）作为潜在的端粒酶抑制剂 一些癌症被认为源自端粒酶活性的增强，端粒酶催化端粒DNA末端的延伸。由于端粒酶不能与 G 四联体结构结合，因此能够稳定这种 DNA 结构的化合物是端粒酶抑制剂的良好候选者。我们测试了与 DNA 相互作用的 TAP 对端粒酶的抑制能力。 TAP 具有 G-四重体结构的显着稳定能力，因此有望作为新型端粒酶抑制剂。

项目成果

Bernard Juskowiak: "Spectral properties and binding study of DNA complexes with a rigid bisintercalatorl, 4-bis ((N-methylquinolinium-4-yl) vinyl) benzene"Spectrochimica Acta Part A. 59. 1083-1094 (2003)

Bernard Juskowiak：“DNA 复合物与刚性双嵌入剂、4-双 ((N-甲基喹啉鎓-4-基) 乙烯基) 苯的光谱特性和结合研究”Spectrochimica Acta Part A. 59. 1083-1094 (2003)

H.Ueyama: "Tetrakis-acridinyl peptide : a novel fluorometric reagent for nucleic acid analysis based on the fluorescence dequenching upon DNA binding"Analyst. 127. 886-888 (2002)

H.Ueyama：“四吖啶基肽：一种基于 DNA 结合荧光去猝灭的核酸分析新型荧光试剂”分析员。

K.Yamashita et al.: "Analysis of the complex of oligonucleotide duplexes with ligands by MALDI-TOF Mass Spectroscopy"Chem. Lett. 680-681 (2001)

K.Yamashita 等人：“通过 MALDI-TOF 质谱分析寡核苷酸双链体与配体的复合物”Chem。

Shigeori Takenaka: "Small Molecule DNA and RNA Binders : From Synthesis to Nucleic Acid Complexes"S, M. Demeunynck, C. Bailly, W.D.Wilson Eds., Wiley-VCH. 22 (2003)

Shigeori Takenaka：“小分子 DNA 和 RNA 结合剂：从合成到核酸复合物”S、M. Demeunynck、C. Bailly、W.D.Wilson Eds.、Wiley-VCH。

B.Juskowiak: "Detection of noncovalent interactions of hairpin oligonucleotide with stilbazolium ligands by MALDI TOF mass spectrometry"International Journal of Mass Spectrometry. 229. 225-230 (2003)

B.Juskowiak：“通过 MALDI TOF 质谱法检测发夹寡核苷酸与 stilbazolium 配体的非共价相互作用”国际质谱杂志。