Bioorganic Reactivity: Patterns, Principles and Applications

我建议我的学生和我一起进行有趣而有意义的研究，这项研究是在化学和生物的交汇处进行的。我们有三个主要感兴趣的领域。在其中一个课程中，我们学习了生物系统如何能够与原本稳定的化合物产生二氧化碳。我们将研究具有与酶相关的特征的化合物。这使我们能够比较价格和产品。这些相似之处和不同之处揭示了这种酶的关键部分。我们专注于通过将反应化合物与维生素B1的衍生物结合而形成中间体的酶。这些酶改变了会失去二氧化碳的化合物的反应性。我们可以在没有酶的情况下跟踪准确的成分，从而导致路径较慢和产生不同的产品。这种对比使我们能够专注于说明差异的详细步骤。我们将研究这些差异的后果。我们要学的第一件事是这种酶如何在蛋白质的帮助下加速这一过程。然后从这一课中，我们将开发出在没有蛋白质的情况下工作的改进的反应。我们想要找出二氧化碳是如何由于新陈代谢而非常迅速地释放出来的，这在生命系统中是常见的，而没有酶的相同化合物是持久存在的。我们将测试一些想法，通过这些想法，我们可以在溶液反应中获得与酶类似的结果。通过这些努力，学生们将获得原本无法获得的洞察力。我们的方法包括在非酶反应系统中添加一种捕获成分(一种辅助酸)，这种成分可以阻止二氧化碳的回流，就像它在酶上发生的那样。这应该会提高没有酶的整个过程的速度，因此没有酶的反应会更快。这为学生提供了多样化的知识、发展推理的挑战和宝贵的技术技能。我们还在化学与生物相互作用的其他领域开展工作。我们正在开发新的化学合成方法，这种方法将允许添加非天然氨基酸来取代蛋白质中的氨基酸。这将在核糖体中产生含有非天然氨基酸成分的蛋白质。这将使新的蛋白质具有有用的性质和许多应用。我们将开发新的化学反应，将非天然氨基酸添加到转移RNA上，转移RNA将它们携带到核糖体中，然后添加到核糖体中形成蛋白质。我们还将使用相同的方法来修改碳水化合物，以用作在特定位置改变的材料。最后，我们正在开发方法，允许天然氧气载体血红蛋白在溶液中的红细胞外存活，就像在循环中取代红细胞一样。这样的产品将有许多应用，从红细胞替代品到用于灌流的氧气载体。我们的方法是从不用于输血的红细胞中提取血红蛋白，并将其转化。

I propose that my students and I will do interesting and significant research that is at the intersection of chemistry and biology. We have three principal areas of interest. In one, we learn how biological systems are able to produce CO2 with compounds that are otherwise stable. We will study compounds with characteristics that relate to those in enzymes. This allows us to compare the rates and products. The parallels and differences reveal the critical parts of the enzyme. We focus on  enzymes that form intermediates derived from combining the reacting compound with a derivative of  vitamin B1. The enzymes change the reactivity of the compound that will lose CO2. We can follow the exact components without an enzyme that lead to a slower path and different products. This contrast allows us to focus on the detailed steps that account for the difference. We will examine the consequences of those differences. The first thing we will learn is how the enzyme, with the aid of a protein, speeds up the process. Then from that lesson, we will develop improved reactions that work without the protein. We want to find how CO2 is released very rapidly as a result of metabolism, a common occurrence in living systems, while the same compounds without an enzyme are persistent. We will test ideas by which we may achieve a similar outcome in a solution reaction as occurs on the enzyme. Through these efforts, the students will gain insights that would not have otherwise accessible. Our approach involves adding a trapping component (an auxiliary acid) to the nonenzymic reaction system that could block the return of CO2, as it would occur on the enzyme. This should enhance the rate of the overall process without the enzyme and therefore produce more rapid reactions without the enzyme. This gives students diverse knowledge, challenges that develop reasoning, and valuable technical skils.  We also work in other areas where chemistry interacts biology.  We are developing new chemical  methods that will allow the addition  of unnatural amino acids in place of amino acids in proteins. This will create  proteins in ribosomes with unnatural amino acid components. This would make new  proteins with useful properties and many applications. We will do this by developing new chemical reactions that add the unnatural amino acids onto transfer RNA, which carries them into the ribosome where then are added to form a protein. We also will use the same method to modify carbohydrates for use as materials that are altered at specific sites. Finally, we are developing ways to allow the natural oxygen carrier,  hemoglobin, to survive outside red blood cells in solutions, as in circulation in place of red blood cells. Such a product would have many applications, from red cells replacements, to oxygen carriers for perfusion. Our approach takes hemoglobin from red cells that are not used for transfusions and convert them.