I attended Dr. Courtney Aldrich's seminar on November 15. He was from the Medicinal Chemistry Department of the University of Minnesota. The topic of his talk was designing antibiotics that would target biotin metabolism in Mycobacterium tuberculosis. I will go ahead and admit that the majority of his talk was way over my head. There were moments where he would talk about things that were heavily microbiological and I understood these moments because I have taken microbiology. However, the organic chemistry sections were a good bit past my understanding.
To start off his talk his first discussed the history of the discovery of various antibiotics. He told us that during the 1940's-1960's there were a myriad of antibiotics discovered but there have been no huge discoveries since 1987. Dr. Aldrich then went over the different methods that antibiotics can use to "destroy" bacteria. These include interrupting cell wall synthesis and blocking transcription of proteins. He then reviewed the strategies and challenges in developing antibiotics for drug use. He mentioned that there were two different methods of doing so: unbiased and biased.
Dr. Aldrich then discussed why biotin was an important molecule to focus on for TB. Biotin is a cofactor that catalyzes the first step in fatty acid biosynthesis. Fatty acids are the building blocks for lipids. Lipids play an important role in the cell envelope of cells in the Mycobacterial family. This unique cell envelope is what helps contribute to their robustness in response to antibiotics. An antibiotic that could target the cell envelope could be very effective against M. tuberculosis.
After this point I began to become lost because this is where the biological portion ended and the organic chemistry of an portion began. He showed a synthesis of an aromatization inhibitor. He then discussed how dihydropyridane irreversibly inhibits BioA. Next a BioA continuous coupled assay was done with DTB fluorescence displacement. After that a whole cell assay was done.
In part three Dr. Aldrich discussed how biotinyl-adenosine monosulfamate was unstable and how that could be fixed. He also discussed how that the newly found antibiotic agents were screened against TB and other Gram + and Gram - bacteria. The results showed that it did not have the same results in other types of bacteria.