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: 6219060
• 负责人: EDWIN NOMBRES QUINONES
• 金额: $ 0.94万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219060
• 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(CDS)的空腔能形成主客体(HG)络合物 具有多个底物，包括带电分子和中性分子 物种。(1‘2)然而，Cd底物络合物的形成可能涉及 过程而不是简单地绑定到空洞。衍生品CDS有 已经准备好，表明附加的组可以参与 在镉与底物的络合作用中。此外，分子的底物 比CD腔大的尺寸可能会绑定到腔外。近期工作 证明了电荷转移态(A*) 对二甲氨基苯甲腈(DMABN)的状态)结合在β-之外- 环糊精(β-CD)，而中性激发态(B*态) 形成HG络合物。这一发现强调了这样一个事实 HG复合体不一定是更稳定的复合体 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发挥重要作用。 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，他们与底物的相互作用模式不能 先验的已知或先验预测的 本研究的设计是在这样一个前提下进行的 开发的研究Cd-衬底系统的方法可能是 扩展以进一步理解涉及配基的相互作用 和生物医学相关的蛋白质。应该指出的是，由于 蛋白质的构象可变性是很难测量的 蛋白质-配体结合常数在很大的温度范围内。 此外，由于表面残留物种类繁多， 可导致蛋白质-配体的非特异性相互作用的数量 绑定可以非常大。拟议的研究代表了一项独特的 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 衬底与CD腔之间的相互作用及其比较 这些与那些发生在相对简单的 这种分子的表面。这样的比较应该代表一个 向理解导致复杂性的机制迈出重要一步 形成，因此提供了关于 生物分子中更复杂的相互作用。这个 底物形成H-G络合物可能改变其辐射 寿命、激发态能量、热和光化学反应活性 我们可以监测这些变化，以获得关于大自然的信息 在这些互动中。确定了各种CD的性质-- 底物络合物在预测药物稳定性方面可能很重要。 使用计算机模型和用于设计底物-酶复合体 强效的酶抑制剂。