BIOCHEMICAL MODEL REACTIONS

这个项目的部分目的是开发一种化合物，它可以在水溶液中与肽和蛋白质结合，并对其结构进行特定的识别。化合物是由两个或三个笼式成分组成的，每个笼式成分都可以结合一个氨基酸侧链，以及其他单元与带电基团相互作用。选择性结合物可以直接导致新的药物化合物，因为它们可以阻止激素与受体的结合，或者蛋白质之间的结合。这种结合在许多疾病中具有有用的生物学效应：多肽与其受体的结合——或者蛋白质以二聚体或聚集体的形式相互结合——是许多生物过程的重要方面，包括不希望发生的过程。该项目的第二部分涉及发明和研究模仿酶的新型催化剂。它提供了与理解生物化学相关的简单化学，这种理解经常被用作新药物开发的指导。此外，在自然中进行的化学比相关的非生物化学更有效，更有选择性。模仿生物化学的选择性化学的发展在化学合成，包括药物合成方面有很大的用处。酶通常通过利用疏水性和其他作用力结合底物来催化反应，然后用两个或两个以上的催化基团（来自蛋白质侧链或辅酶）催化特定所需的反应。在这个项目中，结合将与现成的环糊精或其他合成腔分子进行，而催化将与酸/碱基团，辅酶基团或金属离子进行。期望通过调整催化剂/底物配合物的几何关系可以制备出良好的催化剂，这将有助于我们理解酶快速催化的原因。它还将帮助我们设计有用的催化剂。它们本身可能被证明是有用的药物，取代或增强天然酶的催化作用。为了使这成为可能，重要的是它们在水溶液中起作用，因为它们被设计成这样。

This project is aimed in part at developing compounds that can bind to peptides and proteins in water solution with specific recognition of their structures. Compounds are being made that are comprised of two or three cage components, each of which can bind an amino acid sidechain, along with other units to interact with charged groups. Selective binders could be direct leads into novel medicinal compounds, since they would block the binding of hormones to receptors, or of proteins to each other. Such binding could have useful biological effects in many disease: the binding of peptides to their receptors-or of proteins to each other in dimmers or aggregates-are important aspects of many biological processes, including undesirable ones. The second part of the project deals with the invention and study of novel catalysts that imitate enzymes. It furnishes the simple chemistry relevant to understanding biological chemistry, and such understanding is frequently used as a guide in the development of new medicinals. Also, the chemistry performed in Nature is more effective and more selective than has yet been achieved with related non- biological chemistry. The development of selective chemistry that imitates biological chemistry could be of great use in chemical synthesis, including the synthesis of medicinals. Enzymes typically catalyze reactions by binding their substrates, using hydrophobic and other forces, and then catalyzing the specific needed reaction with two or more catalytic groups, either from the protein sidechains or from coenzymes. In this project the binding will be done with readily available cyclodextrins, or with other synthetic cavity molecules, while the catalysis will be done with acid/base groups, with coenzyme groups, or with metal ions. It is expected that good catalysts can be produced by adjusting the geometric relationships in the catalyst/substrate complexes, and that this will help us understand the reason for rapid catalysis by enzymes. It will also help us design useful catalysts. They may prove to be useful medicinals in their own right, replacing or augementing catalysis by natural enzymes. For this to be possible, it is important that they function in water solution, as they are designed to do.