Drug-DNA Interaction---Base Sequence Selectivity

药物-DNA相互作用---碱基序列选择性

• 批准号: 02670985
• 负责人: TSUBOI Masamichi
• 金额: $ 1.6万
• 依托单位: Iwaki-Meisei University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670985/
• 关键词: DNA; Drug-DNA interaction; Stopped flow; Intercalation; Groove-binding; Fluorescence spctroscopy; Raman spectroscopy; Translocation along DNA; アクラシノマイシン; 結合反応速度; 解離反応速度; ヘキスト33258; アドリアマイシン; DNA・薬剤の結合; アンキノマイシン; ヘダマイシン; ディスタマイシン; ラマンスペクトル

DNA interacts with a variety of smaller molecules including antibiotics, calcinogens and biological stains. Many of these have been developed as drugs. Elucidation of the detailed molecular and electronic mechanisms of such interactions has been attempted, because it is considered to be essential, not only for the development of drug chemistry itself, but also for establishing useful examples of gene decoding interactions. A drug or related small molecule can also be regarded as a chemical probe of the force field existing in the vicinity of its nucleic acid binding site.Extensive studies by means of ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, Raman spectroscopy. circular dichroism, and NMR, in combination with stopped flow, electrophoresis, electron microscopy, and flow dichroism experiments, have shown that there are two modes of binding distinguish-able : intercalation between stacked bases (B1) and groove binding (B2). Besides such firm bindings, however, every drug has been found to have a loose interaction (E) which can be detected through a fluorescence change. It has been found that in general the E interaction is stronger with the GC portion than with the AT portion. For B1, GC>AT, and for B2, GC<AT.In the course of our Raman study, an interesting fact has been found which indicates the translocation of a legand from an intercalation site (GC, B1) into a groove-binding site (AT, B2) along the double-helical DNA chain, A water soluble Cu-porphyrin binds through an intercalation at a GC portion, but on a laser irradiation it goes into an ATAT groove.

DNA与各种较小的分子相互作用，包括抗生素，calcinogens和生物染色剂。其中许多已被开发为药物。这种相互作用的详细的分子和电子机制的阐明已被尝试，因为它被认为是必不可少的，不仅为药物化学本身的发展，而且为建立基因解码相互作用的有用的例子。药物或相关的小分子也可以被看作是其核酸结合位点附近存在的力场的化学探针。通过紫外光谱、荧光光谱、红外光谱、拉曼光谱等手段进行了广泛的研究。圆二色性和NMR，结合停止流动、电泳、电子显微镜和流动二色性实验，已经表明存在两种可结合的模式：堆叠碱基之间的插入（B1）和沟结合（B2）。然而，除了这种牢固的结合之外，已经发现每种药物都具有松散的相互作用（E），其可以通过荧光变化来检测。已经发现，一般来说，E与GC部分的相互作用比与AT部分的相互作用更强。在我们的拉曼研究过程中，发现了一个有趣的事实，即配位体从插入位点（GC，B1）沿着双螺旋DNA链沿着进入沟结合位点（AT，B2）。

项目成果

M.Tsuboi, K.Ushizawa and T.Ueda: "Assinments of Raman tensors to Raman bands of nucleic acids : use of a single crystal of adenosine triphosphoric acid and DNA fiber" Nucleic Acids Res.Symp.Ser. 27. 61-62 (1992)

M.Tsuboi、K.Ushizawa 和 T.Ueda：“拉曼张量与核酸拉曼带的分析：使用三磷酸腺苷和 DNA 纤维的单晶”Nucleic Acids Res.Symp.Ser。

坪井 正道: "DNAの解読速度" パリティ. 1991ー06. 36-42 (1991)

Masamichi Tsuboi：“DNA解码速度”1991-06（1991）。

G.J.Thomas and M.Tsuboi: "Raman Spectroscopy of Nucleic Acids and Their Complexes in “Advances in Biophysical Chemistry"C.A.Bush(Ed.)Vol.3,P.1-69" JAI Press Inc.Greenwich,Connecticut,U.S.A., 69 (1993)

G.J.Thomas 和 M.Tsuboi：“《生物物理化学进展》中的核酸及其复合物的拉曼光谱”C.A.Bush（主编）第 3 卷，第 1-69 卷”JAI Press Inc.Greenwich, Connecticut,U.S.A., 69 (1993)

G.J.Thomas and M.Tsuboi: "Raman Spectroscopy of Nucleic Acids and Their Complexes" Advances in Biophysical Chemistry C.A.Bush (Ed.). Vol.3. p1-69 (1993)

G.J.Thomas 和 M.Tsuboi：“核酸及其复合物的拉曼光谱”生物物理化学进展 C.A.Bush（主编）。

J.M.Benevides,M.Tsuboi,A.H.-J.Wang and G.J.Thomas: "Local Raman Tensors of Double-Helical DNA in the Crystal:A Basis for Determining DNA Residue Orientations" Journal of American Chemical Society. (1993)

J.M.Benevides、M.Tsuboi、A.H.-J.Wang 和 G.J.Thomas：“晶体中双螺旋 DNA 的局部拉曼张量：确定 DNA 残基方向的基础”美国化学会杂志。