SELF-ORGANIZING MOLECULAR RECEPTOR DESIGN

我的研究计划的长期目标是了解如何 设计高选择性的抗体样结合部位和酶样结合部位 催化剂。分子识别是一个快速发展的领域，因为 对生物分子的了解将通过以下方式获得 学习更简单、定义明确的结构以及演示的 特定结合物质用于分离、运输、 分析、结构组织和催化。基本上都是 药物是一种专门识别一种 生理上相关的目标。 模型化合物对生物系统的研究很有用，因为 它们允许分离特定的因素以确定它们的相对 重要性。本申请中提出的研究目标 是准备模型化合物来探索金属的有效性- 组织结合位点的配基相互作用和电荷(Pi)效应 以定向衬底。这将导致有趣和有用的 受体，以及对其重要性的更多认识 自然系统中的这些因素。 我们有三个具体目标：1.进一步表征自我 我们已经展示的组装的金属络合物将结合中性芳香族化合物 客人们。我们期待着有趣的合作绑定，如下所示 复合体，就像自然系统一样，可以利用金属在 既是结构性的，也是功能性的。2.利用我们的自我-- 结合位点设计中的组织策略 癌基因衍生的蛋白激酶的磷酸酪氨酸产物。我们希望 展示了这种底物通过自结合的优势 有组织的受体胜过更简单的分子受体。3.进一步扩展 电荷方向性的最新结果和理解-(Pi) 利用电荷相互作用获得结合基片的取向 (PI)和供体-受体相互作用。这涉及到对边界的控制 通过一种先前未讨论过的机制对客人进行定向。

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.