SELF-ORGANIZING MOLECULAR RECEPTOR DESIGN

自组织分子受体设计

• 批准号: 2185168
• 负责人: ALAN W. SCHWABACHER
• 金额: $ 7.87万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185168
• 关键词: chemical synthesis; drug design /synthesis /production; electron density; high performance liquid chromatography; ligands; mass spectrometry; metal complex; molecular biology; molecular polarity; molecular site; nuclear magnetic resonance spectroscopy; phosphoproteins; receptor; receptor binding; tyrosine

The long term objectives of my research program are to understand how to design highly selective antibody-like binding sites and enzyme-like catalysts. Molecular recognition is a rapidly growing field because of the increased understanding of biological molecules to be gained by studying simpler, well-defined, structures, as well as the demonstrated utility of specifically binding substances for separation, transport, analysis, structural organization, and catalysis. Essentially all pharmaceuticals are substances which specifically recognize a physiologically relevant target. Model compounds are useful to the study of biological systems because they allow isolation of specific factors to determine their relative importance. The objective of the research proposed in this application is to prepare model compounds to probe the effectiveness of metal- ligand interactions to organize binding sites, and charge-(pi) effects to orient substrates. This will lead to interesting and useful receptors, as well as to an increased appreciation for the significance of these factors in natural systems. We have three specific aims: 1. To characterize further the self- assembled metal complexes that we have shown will bind neutral aromatic guests. We anticipate interesting cooperative binding as these complexes, like the natural systems, can use the metals in a structural, as well as a functional role. 2. To use our self- organization strategy in the design of binding sites for phosphotyrosine products of oncogene-derived kinases. We hope to demonstrate advantages for the binding of such substrates by self- organized receptors over simpler molecular receptors. 3. To expand on our recent results and understanding of directionality of charge-(pi) interactions to obtain orientation of bound substrates using charge- (pi) and donor-acceptor interactions. This involves control of bound guest orientation by a mechanism not previously discussed.

我的研究计划的长期目标是了解如何 设计高度选择性的抗体样结合位点和酶样结合位点， 催化剂的分子识别是一个快速发展的领域，因为 对生物分子的理解， 研究更简单，定义明确的结构，以及证明 特异性结合物质在分离，运输， 分析、结构组织和催化。基本上所有 药物是专门识别 生理相关的目标。 模型化合物对于生物系统的研究是有用的，因为 它们允许隔离特定因素以确定其相对 重要性本申请中提出的研究目的 是制备模型化合物来探测金属- 组织结合位点的配体相互作用和电荷（pi）效应 以定向衬底。这将导致有趣和有用的 受体，以及对重要性的日益认识， 这些因素在自然系统中。 我们有三个具体目标：1。为了进一步描述自我- 组装的金属络合物，我们已经表明，将结合中性芳族 客人我们期待有趣的合作绑定，因为这些 复合物，像自然系统一样，可以在一个特定的环境中使用金属。 结构性和功能性作用。2.利用我们的自我- 结合位点设计的组织策略 癌基因衍生激酶的磷酸酪氨酸产物。我们希望 证明了通过自- 有组织的受体而不是简单的分子受体。3.扩张 我们最近的结果和对电荷方向性的理解-（π） 相互作用，以获得使用电荷的结合基板的取向， (pi)和供体-受体相互作用。这涉及到对约束的控制 通过先前未讨论的机制进行客体取向。