NEW STUDIES IN MOLECULAR RECOGNITION

分子识别的新研究；结合的人工“宿主” 特定的“客人”有巨大的潜力造福人类健康。这个 我们在主客体化学/分子方面工作的主要、持续的目标 认可是发现原则和战略，这些原则和战略将增强 了解弱的非共价相互作用并促进其 应用于具有生物医学意义的问题。在下一次预算中 期间，我们建议通过研究宿主来实现此目标 复杂的宾客使用氢键或pi堆叠在三个非常 不同环境：(1)在层析载体表面，(2) 在双螺旋DNA的主槽中，以及(3)树枝状大分子内部。 随着药物设计的组合方法的出现和对药物的使用 分子识别研究的其他领域中的组合方法， 对快速和准确的约束措施的需求越来越大 亲和力。一个项目将决定以前的 同时测定游离络合离子的高效液相色谱方法 多个客体/分析物的能量和热焓。为此， 将开发几种新的化学键合固定相(CBSP) 使用使客人在包括水在内的极性溶剂中复杂化的东道主。 第二个项目涉及开发GC和AT碱基对的宿主，该宿主 可以识别DNA三链中的嘧啶。因此，新的DNA碱基将 能够同时合成氢键和氢键 AT或GC碱基对的碱基。这些新的碱基将被核糖化， 转化为亚磷酰胺，并结合成寡核苷酸 DNA合成的自动化方法。这些碱基的测序能力 通过形成三螺旋选择性识别双螺旋DNA 将会被确定。这项工作的目标是一种通用的方法 通过三链形成进行序列特异性DNA识别。这个 潜在的序列选择性三链形成对基因的调控 生物医学应用具有巨大的意义。 最后一个项目涉及合成和研究下列宿主 周围都是树枝。这些树枝状宿主可能具有相对 不变的微环境，使它们能够在广泛的 溶剂，包括水。这种结构最终可能会起到非常重要的作用 特定的药物运送工具。

New Studies in Molecular Recognition; Synthetic "hosts" that bind particular "guests" have tremendous potential to benefit human health. The major, continuing objective of our work in host-guest chemistry/molecular recognition is to discover principles and strategies that will enhance understanding of weak noncovalent interactions and facilitate their application to problems of biomedical significance. In the next budget period, we propose to accomplish this objective by studying hosts that complex guests using hydrogen bonding or pi-stacking in three very different environments: (1) on the surface of chromatographic supports, (2) in the major groove of double helical DNA, and (3) inside dendrimers. With the advent of combinatorial approaches to drug design and the use of combinatorial methods in other areas of molecular recognition research, there is an increasing demand for rapid and accurate measures of binding affinities. One project will determine the generality of a previously developed HPLC method of simultaneously measuring complexation free energies and enthalpies of multiple guests/analytes. Toward this end, several new chemically bonded stationary phases (CBSPs) will be developed using hosts that complex guests in polar solvents including water. A second project involves developing a host for GC and AT base-pairs that can recognize pyrimidines within a DNA triplex. Thus, new DNA bases will be synthesized that are capable of simultaneously hydrogen bonding both bases of an AT or GC base-pair. These novel bases will be ribosylated, converted to phosphoramidites, and incorporated into oligonucleotides using automated methods of DNA synthesis. The ability of these bases to sequence selectively recognize double helical DNA through triple-helix formation will be determined. The objective of this work is a general method of sequence-specific DNA recognition through triplex formation. The regulation of genes by sequence selective triplex formation ia a potential biomedical application of tremendous significance. A final project involves the synthesis and study of hosts that are surrounded by dendrons. These dendritic hosts may have a relatively invariant microenvironment that allows them to function in a wide range of solvents, including water. Such structures may ultimately serve as highly specific drug delivery vehicles.