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）的空腔可以形成主客体（HG）复合物 具有许多底物，包括带电和中性分子 物种（1 '2）然而，CD-底物复合物的形成可涉及 除了简单的结合到腔体之外的过程。衍生CD具有 已经准备好，表明附加组可以参加 在CD-底物复合物中。此外，分子的底物 尺寸大于CD腔的材料可能会在腔外结合。最近的工作 从我们的小组证明，电荷转移状态（A* 状态）的对二甲氨基苯甲腈（DMABN）结合的β- 环糊精（β-CD），而中性激发态（B* 态） 形成HG复合物。这一发现强调了一个事实， HG复合物不一定是更稳定的， 溶剂化效应和衬底的电荷分布起着重要的作用。 在涉及弱相互作用的结合过程中起重要作用。 从这一信息中可以明显看出，尽管CD可以被视为 非常简单的宿主，它们与底物的相互作用模式不能被 已知的或者预先预测的。 本研究的设计前提是， 和方法开发调查光盘基板系统可能是 扩展到进一步了解涉及配体的相互作用 和生物医学相关的蛋白质。应当指出，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。 此外，由于表面残留物种类繁多， 可导致蛋白质-配体相互作用的非特异性相互作用的数量 绑定可以非常大。这项研究提出了一个独特的 获取最基本参数信息的方法 这会影响复合物的形成我们将确定 基板和CD腔之间的相互作用，并比较 这些相互作用发生在相对简单的 这个分子的表面。这种比较应该代表一种 向理解导致复杂的 形成，并因此提供有用的信息， 生物分子中更复杂的相互作用。的 由底物形成的H-G复合物可以改变其辐射特性。 寿命、激发态能量、热和光化学反应性 我们可以通过监测这些变化来获取 这些互动。确定各种CD的性质- 底物复合物在预测 底物酶复合物的计算机模型和设计 有效的酶抑制剂