SELECTIVE METAL ORGANIZED SYNTHETIC RECEPTORS

选择性金属组织合成受体

• 批准号: 2825056
• 负责人: ALAN W. SCHWABACHER
• 金额: $ 4.91万
• 依托单位: UNIVERSITY OF WISCONSIN MILWAUKEE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2825056
• 关键词: binding sites; biomimetics; conformation; drug receptors; metal complex; molecular assembly /self assembly; protein engineering; protein structure function; receptor binding; stereochemistry; synthetic peptide

DESCRIPTION: (Verbatim from the Applicant's Abstract) Most pharmaceuticals are small molecules that bind to concavities in large molecular target sites. The scarcity of drugs that act like binding pockets (e.g., Vancomycin) is not an indication of their lack of utility: antibodies, for example, are very useful. However, chemistry lags in its ability to design useful smaller, simpler binding pockets. The ability to target a small molecule or arbitrary location on an enzyme or receptor would increase the strategies available for pharmaceutical development. Long term objectives of my research are to design and prepare synthetic antibody-like binding sites and enzyme-like catalysts with predetermined specificity. We propose here a family of host molecules, each assembled or organized by a metal, to bind polyfunctional organic guests. The metals provide effective methods for building complex structures rapidly, controlling their shapes and presentation of functional groups, and making small perturbations to the structures. A key to selectivity is the cooperation of multiple binding interactions. As measured by effective molarity (EM) values, our receptors are outstanding. We plan to probe the generality of these large EM values. This will lead to interesting and useful receptors, as well as to an increased appreciation of the significance of these factors in natural systems. Specific aims: 1. To generalize and characterize further the self- assembled metal complexes that we have shown will ditopically bind guests. As we modify metals and ligands, we will evaluate the effect on these EM values, which will assist our ability to design a specific binding site. 2. To demonstrate molecular templating for stereochemical control of the construction of well defined host molecules. We aim to demonstrate control of cavity shape, as well as of orientation of binding groups and appendages.

产品说明：（逐字引用自申请人的摘要）大多数药物是小分子，其结合到大分子靶位点中的凹部。缺乏像约束口袋一样起作用的药物（例如，万古霉素）并不表明它们缺乏效用：例如，抗体是非常有用的。然而，化学在设计有用的更小、更简单的结合口袋方面的能力滞后。靶向酶或受体上的小分子或任意位置的能力将增加可用于药物开发的策略。本研究的长期目标是设计和制备具有预定特异性的合成抗体样结合位点和酶样催化剂。我们在这里提出了一个家庭的主机分子，每个组装或组织的金属，绑定多功能有机客人。金属提供了快速构建复杂结构、控制其形状和官能团的呈现以及对结构进行小扰动的有效方法。选择性的关键是多种结合相互作用的合作。通过有效摩尔浓度（EM）值测量，我们的受体非常出色。我们计划探索这些大EM值的普遍性。这将导致有趣的和有用的受体，以及对这些因素在自然系统中的重要性的认识。具体目标：1.为了进一步推广和表征我们已经证明的自组装金属配合物与客体的双拓扑结合.当我们修饰金属和配体时，我们将评估对这些EM值的影响，这将有助于我们设计特异性结合位点的能力。2.证明分子模板用于构建明确定义的宿主分子的立体化学控制。我们的目标是展示腔形状的控制，以及结合基团和附属物的方向。