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: 2756051
• 金额: $ 0.24万
• 依托单位: UNIVERSITY OF PUERTO RICO RIO PIEDRAS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2756051
• 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 具有多种底物，包括带电和中性分子 (1'2) 然而，CD-底物复合物的形成可能涉及 除了简单地粘合到空腔之外的过程。衍生CD有 已准备好表明附加组可以参加 在CD-底物络合中。此外，分子底物 大于CD空腔的尺寸可能会在空腔之外结合。最近的工作 我们小组证明了电荷转移状态（A* 对二甲氨基苯甲腈 (DMABN) 的状态）在 β- 外部结合 环糊精（β-CD），而中性激发态（B*态） 同一分子的 HG 复合物形成。这一发现强调了一个事实 HG 复合体不一定是更稳定的复合体并且 溶剂化效应和基底的电荷分布起着 在涉及弱相互作用的结合过程中发挥重要作用。 从该信息可以明显看出，虽然 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 先验已知或预测的。 本研究是在以下前提下设计的： 研究 CD 基底系统的方法和方法可以是 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。应该指出的是，由于 蛋白质构象的变异性，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-配体的非特异性相互作用的数量 绑定可能非常大。拟议的研究代表了独特的 获取有关最基本参数信息的方法 这可能会影响复杂的形成。我们将确定的性质 基底和 CD 腔之间的相互作用并进行比较 这些相互作用与那些相对简单的相互作用发生 该分子的表面。这种比较应该代表 理解导致复杂机制的重要一步 形成并因此提供有关的有用信息 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 寿命、激发态能量、热和光化学反应性 我们可以监控这些变化以获取有关自然的信息 这些相互作用。确定各种 CD 的性质 底物复合物对于预测其稳定性可能很重要 使用计算机模型和设计底物-酶复合物 有效的酶抑制剂。