SELECTIVE METAL ORGANIZED SYNTHETIC RECEPTORS

描述：（摘自申请人摘要）大多数药物都是小分子，与大分子靶点的凹陷结合。像捆绑袋一样的药物（如万古霉素）的缺乏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、更简单的装订袋方面落后了。靶向酶或受体上的小分子或任意位置的能力将增加药物开发的可用策略。我的长期研究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宿主分子家族，每个宿主分子都由金属组装或组织，以结合多功能有机客体。金属为快速构建复杂结构、控制其形状和官能团的呈现以及对结构产生微小扰动提供了有效的方法。选择性的关键是多种结合相互作用的合作。通过测量有效摩尔浓度（EM）值，我们的受体是杰出的。我们计划探索这些大EM值的普遍性。这将导致有趣和有用的受体，以及增加对这些因素在自然系统中的重要性的认识。具体目标：1；为了进一步概括和表征我们所展示的自组装金属配合物将双视结合客体。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定结合位点的能力。2. 演示分子模板的立体化学控制结构明确的宿主分子。我们的目的是证明控制腔的形状，以及方向的结合基团和附件。

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.