Master of Science (MS)
Biotin is an essential growth factor found in all living cells. It functions as a cofactor for a group of coenzymes that catalyze transcarboxylation, decarboxylation, and carboxylation reactions. Acetyl CoA carboxylase catalyzes the first committed and regulated step in fatty acid synthesis in which malonyl CoA is the product. The biotin-dependent enzyme is found in all animals, plants, and bacteria. We studied the kinetic and structural aspects of acetyl CoA carboxylase, and in 1999 we reported the bioactivity and total synthesis of a unique first generation biotin-derived inhibitor of acetyl CoA carboxylase, 1(BP1). Kinetic studies on the activity of E. coli biotin carboxylase yielded an inhibition constant of 8.4±1 mM. Since that time, we have improved the yield and purification of 1. Currently, we are designing multisubstrate analogs which involve the attachment of adenosine moieties at the 1-N of biotin. We reason that these compounds will have a greater affinity for acetyl CoA carboxylase. In addition, we are synthesizing biotin derivatives for their study in three main areas: (1) understanding the mechanism of biotin carboxylase and acetyl CoA carboxylase for the development of new therapeutic agents, (2) screening for ribozyme activity to support the “RNA World” hypothesis, and (3) investigation of chiral cationic micelles for analytical separations.
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Johnson, Latisha Chanette, "The synthesis of new biotin derivatives and their bioactivity" (2002). LSU Master's Theses. 1511.