Bioorganic Reactivity: Patterns, Principles and Applications

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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.