Dynamics of molecular recognition

分子识别动力学

• 批准号: 04101003
• 负责人: OGOSHI Hisanobu
• 金额: $ 160万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04101003/
• 关键词: Molecular Recognition; Porphyrin; Chiral Recognition; Electron Transfer; Thermodynamic Parameter; Conformation; Solvent Effects; 熱力学パラメーター; 円偏光ニ色性; 電子移動反応; 水素結合; キノン; シクロデキストリン; ヌクレオチド; アミノ酸; シクロデモストリン; ユビキノン

We have studied four topics to elucidate the dynamics of molecular recognition : (1) Conformational changes induced by molecular recognition, (2) Thermodynamic and spectroscopic studies of multi-point molecular recognition, (3) Electron transfer process regulated by molecular recognition, and (4) Fluoroporphyrins and reconstituted myoglobin.1.Induced-fit binding of quinones to tetrahydroxyporphyrin results in the atropisomerization in the porphyrin. Also preorganization of flexible nucleobase receptor before binding a target guest was demonstrated by determining thermodynamic parameters of the binding. Porphyrin dimer formation following atropisomerization was also studied kinetically.2.Circular dichroism was used to investigate the interaction mode of porphyrin-amino acid system. Two-point recognition lead to split-type induced CD,through electrostatic coupling between the chromophores. Novel chiral porphyrins were prepared, which show moderate to high enantioselective binding of amino acid esters. Receptors for tartaric acid, aspartic acid and sugars were also prepared. These receptors showed high regioselectivity for the guest. Enthalpy and entropy changes upon complexation were used to estimate conformational changes during complex formation.3.Fast electron transfer from singlet state of porphyrin to quinone or viologens driven photochemically was realized by designing a binding site for quenchers. Electron transfer from zinc porphyrin in myoglobin to quinone which is attached by a peptide spacer occurred from a singlet state with a rate one order of magnitude slower than in dichloromethane.4.Reconstitution of myoglobin by artificial hemes showed that interactions between heme and apoprotein can be split into contributions from non-polar interactions of 1,2,3,4-alkyl groups and polar interactions of 6,7-propionate groups. The polar interactions between propionate groups and protein was found to stabilize oxyheme.

本文从四个方面对分子识别动力学进行了研究：(1)分子识别引起的构象变化；(2)多点分子识别的热力学和光谱研究；(3)分子识别调控的电子传递过程；(4)氟卟啉和重组肌红蛋白。醌类与四羟基卟啉的诱导配合结合导致卟啉的atropisomerization。此外，通过确定结合的热力学参数，证明了柔性核碱基受体在结合目标客体之前的预组织。对反异构化后卟啉二聚体的形成进行了动力学研究。利用圆二色性研究了卟啉-氨基酸体系的相互作用模式。两点识别通过发色团之间的静电耦合导致分裂型诱导CD。制备了一种新型的手性卟啉，具有中高对映选择性结合氨基酸酯。还制备了酒石酸、天冬氨酸和糖的受体。这些受体对客体具有较高的区域选择性。用络合时的焓和熵变化来估计络合过程中的构象变化。通过设计猝灭剂的结合位点，实现了卟啉单线态到醌或紫罗兰素的快速光化学转移。肌红蛋白中的卟啉锌与醌之间的电子转移发生在单线态，速度比二氯甲烷慢一个数量级。人工血红素对肌红蛋白的重构表明，血红素与载脂蛋白之间的相互作用可分为1,2,3,4-烷基的非极性相互作用和6,7-丙酸基的极性相互作用。丙酸基团与蛋白质之间的极性相互作用被发现稳定氧血红素。

项目成果

T. Mizutani: "Molecular Recognition of Carbohydrates by Zinc Porphyrins." J. Chem. Soc., Chem. Commun.1257-1258 (1995)

T. Mizutani：“锌卟啉对碳水化合物的分子识别”。

H.Ogoshi, Molecular Recognition: "New Chiral Metalloporphyrins as Receptor Models" Supramol.Chem. 6. 115-124 (1995)

H.Ogoshi，分子识别：“新的手性金属卟啉作为受体模型”Supramol.Chem。

Takashi Hayashi: "Synthesis and Structure of a New cis-1,3-Dihydroxycyclohexane Derivative having Four Convergent Hydroxy Groups" J.Chem.Soc.,Chem.Commun.364-365 (1993)

Takashi Hayashi：“具有四个趋同羟基的新型顺式 1,3-二羟基环己烷衍生物的合成和结构”J.Chem.Soc.,Chem.Commun.364-365 (1993)

T.Hayashi: "Relationship between Electron Transfer and Structure of Quinone-Linked Zinc Porphyrin having Flexible Peptide Spacer" J.Chem.Soc.,Chem.Commun.545-546 (1995)

T.Hayashi：“电子转移与具有柔性肽间隔基的醌连接锌卟啉的结构之间的关系”J.Chem.Soc.，Chem.Commun.545-546 (1995)

H.Ogoshi: "Chiral Amino Acid Recongnition on Artificial Receptor Based on Porphyrin" J.Am.Chem.Soc.117. 10950-10957 (1995)

H.Ogoshi：“基于卟啉的人工受体的手性氨基酸识别”J.Am.Chem.Soc.117。