PHOTOPHYSICAL ASSESSMENT OF WEAK INTERACTIONS IN MODELS OF BIOMOLECULAR SYSTEMS

生物分子系统模型中弱相互作用的光物理评估

• 批准号: 6271551
• 负责人: EDWIN NOMBRES QUINONES
• 金额: $ 10.9万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271551
• 关键词: chemical binding; chemical transfer reaction; conformation; cyclodextrins; electronic spectra; enzyme model; fluorescence spectrometry; fluorescent dye /probe; fluorimetry; intermolecular interaction; micelles; photochemistry; thermodynamics

The cavity of cyclodextrins (CDs) can form host-guest (HG) complexes with a number of substrates including charged and neutral molecular species.(1'2) However, formation of CD-substrate complexes can involve processes other than simple binding to the cavity. Derivatized CDs have been prepared which indicate that the appended groups can participate in the CD-substrate complexation. Furthermore, substrates of molecular size larger than the CD cavity may bind outside the cavity. Recent work from our group demonstrated that the charge-transfer state (the A* state) of p-dimethylaminobenzonitrile (DMABN) binds outside of beta- cyclodextrin (beta-CD), while the neutral excited state (the B* state) of the same molecule forms a HG complex. This finding stresses the fact that the HG complex is not necessarily the more stable one and that solvation effects and the charge distribution of the substrate play an important role in the binding processes involving weak interactions. It is apparent from this information that although CDs can regarded as very simple hosts, their mode of interaction with substrates cannot be known or predicted a priori. The present research is designed under the premise that the information and methods developed investigating CD-substrate systems could be extended to further the understanding of interactions involving ligands and biomedically relevant proteins. It should be noted that due to the conformational variability of proteins, it is very difficult to measure the protein-ligand binding constants over large temperature ranges. Also, as a consequence of the great variety of surface residues, the number of non-specific interactions which can lead to protein-ligand binding can be very large. The proposed study represents a unique approach to obtain information concerning the most basic parameters which could affect complex formation. We will establish the nature of the interactions between a substrate and the CD cavity and compare these interactions with those which occur with the relatively simple surface of this molecule. Such comparisons should represent an important step towards understanding the mechanisms leading to complex formation and as a consequence provide useful information concerning the more complicated interactions in biological molecules. The formation of a H-G complex by a substrate may alter its radiative lifetime, excited state energy, thermal and photochemical reactivity and we can monitor those changes to derive information about the nature of these interactions. Establishing the nature of a wide variety of CD- substrate complexes could be important in predicting the stability of substrate-enzyme complexes using computer models and for the design of potent enzyme inhibitors.

环糊精（CD）的腔可以形成宿主 - 吉斯（HG）配合物 具有许多底物，包括带电和中性分子 物种。（1'2）然而，CD-substrate复合物的形成可能涉及 除了简单结合腔以外的过程。衍生的CD具有 已准备好表明附属组可以参加的 在CD-substrate络合中。此外，分子的底物 大于CD腔的尺寸可能会在腔外结合。最近的工作 我们的小组证明了电荷转移状态（a* p-二甲基苯甲硝基硝基（DMABN）的状态）在β-之外结合 环糊精（β-CD），而中性激发态（B*状态） 同一分子形成汞配合物。这一发现强调了事实 HG综合体不一定是更稳定的综合体 溶剂化效果和基板的电荷分布播放 在涉及弱相互作用的结合过程中的重要作用。 从这些信息可以明显看出，尽管CD可以看作 非常简单的主机，它们与基材的互动方式不能是 已知或预测先验。 本研究的设计是在信息的前提下进行的 并且开发了调查CD-substrate系统的方法可能是 扩展以进一步理解涉及配体的相互作用 和生物医学相关的蛋白质。应该注意的是，由于 蛋白质的构象变异性，很难测量 大温度范围内的蛋白质 - 配体结合常数。 同样，由于各种各样的表面残基， 可能导致蛋白质配体的非特异性相互作用的数量 绑定可能很大。拟议的研究代表了一个独特的 获取有关最基本参数的信息的方法 这可能会影响复杂的形成。我们将确定 底物与CD腔之间的相互作用并比较 这些与相对简单发生的相互作用 该分子的表面。这样的比较应该代表 了解导致复杂机制的重要步骤 因此，编队提供了有关的有用信息 生物分子中更复杂的相互作用。这 底物形成H-G复合物可能会改变其辐射 生命周期，激发状态能量，热和光化学反应性 我们可以监视这些更改以得出有关性质的信息 这些相互作用。建立各种CD的性质 底物复合物在预测的稳定性方面可能很重要 使用计算机模型和设计的底物 - 酶复合物 有效的酶抑制剂。