SELF-ORGANIZING MOLECULAR RECEPTOR DESIGN

自组织分子受体设计

• 批准号: 2185170
• 负责人: ALAN W. SCHWABACHER
• 金额: $ 1.27万
• 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/2185170
• 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.

我的研究项目的长期目标是了解如何