Design of Antibiotics that Target Biotin Metabolism

I recently attended a lecture titled "Design of Antibiotics that Target Biotin Metabolism." It was presented by Dr. Courtney Aldrich. Dr. Aldrich is from the University of Minnesota on the Department of Medicinal Chemistry. Dr. Aldrich works in research on antibiotics. He mentioned that the first introduction of antibiotics occurred in 1935. Then from 1945-1960 there was what was considered the "golden age" of antibiotics. This was the time that most of the antibiotics that we have today were created. Since then there has been a severe drought in the synthesis of new antibiotics. Dr Aldrich explained that there are two ways to synthesize antibiotics. The one way was used to create basically all the antibiotics we use is called unbiased-phenotypic whole-cell screening, and then there is another way called biased-target based rationale design. He is currently exploring this other avenue. Dr. Aldrich's research is looking at cofactor biosynthesis as drug targets. Biotin is a common cofactor, involved in lipid biosynthesis, which is important for bacteria to develop a cell wall. His research is working on developing a new antibiotic for Tuberculosis with this other avenue. Tuberculosis is the leading cause of death from bacterial infections. He mentioned that an important part of this target based research is that the target must be validated. This was around the time in the lecture that Dr. Aldrich really started going over my head. He mentioned that they have been trying to treat mice with tuberculosis. He talked a lot about a Bio A. He mentioned some strategies to design inhibitors. He talked about a mechanism based inhibitor that they tried to keep from aromatizing. He also referred to a warhead. At this point in the lecture I just started writing down words that I recognized from class. These included, cis and trans, cyclohexane, Diels-Alder, alkyne, and diastereomer.

Dr. Aldrich is obviously a very brilliant chemist and it sounds like he will hopefully be successful in his research. My only complaint with the lecture is that I wish he had dumbed it down a bit.

The Art of Brewing by Dr. Hamilton

Recently I attended a very engaging presentation by Dr. Tracey Hamilton on "The Art of Brewing". Dr. Hamilton began his presentation by giving some background information on beer. He went on to explain that the earliest types of beers people would drink through a straw because it was from soggy unleavened bread and was called bappir. Dr. Hamilton explained to make hops in beer take water and add yeast which converts sugars to alcohol and carbon dioxide. Next step is to gelatinize the starch, usually around 150 degrees F to accomplish this. The liquid is then separated from the grain by a screen. He also noted that the darker the beer the more acidic it is thus lower the ph level. High amounts of hops in beers can give it a harsh taste however they do have antibacterial properties and people whom drink beers with high amounts of hops usually have fewer cavities. Also if hops beers are not in dark colored bottles they usually have a foul smell because the hops reacts to the sunlight. However if chemically modified hop resins are used, the beer does not have to be placed in dark bottles. Flavors can also be added to beers if they are made a particular way. For example if dimethyl sulfide is used it gives it a cooked corn flavor, lactic acid gives a sour flavor, acetaldehyde gives green apple flavor, and 4-vinyl guiacol gives a clove flavor. Overall the lecture was very entertaining and enjoyable. Dr. Hamilton was very energetic during his presentation and kept the audience engaged with his humor as well. I would definitely recommend sitting in on one of Dr. Hamilton's presentations.    

Dr. Courtney Aldrich on Design of Antibiotics that Target Biotin Metabolism

I attended a seminar taught by Dr. Courtney Aldrich which is based on the design of antibiotic that target biotin metabolism. He is an associate professor in the center for drug design with the University of Minnesota and received his PhD from the University as well. His work is based on the application of antibiotic target on Biotin metabolism with the usage of Mycobacterium tuberculosis, which is an organism found on those with tuberculosis. Being a post-baccalaureate student and with my knowledge of medicinal chemistry due to my years of research with the National Institute of Health, I was very impressed with his lecture. Another topic that intrigued me was the fact that new antibiotics would be developed via the use of unbiased phenotypic whole-cell screening technique that harbor compounds with antibiotic activity and multi-target inhibitors. Dr. Aldrich work is tailored to biotin metabolism in the treatment of tuberculosis. Biotin is a cofactor involved in carboxylation of enzymes and fatty acid biosynthesis that is important to all bacterial cells due to their cell wall structure. Biotin is vital for the mycobacterial cell envelope because it is compose of 70% lipids by weight. Dr. Aldrich’s research focused on specific enzymes in the biotin pathway with emphasizes on Bio enzyme A, a PLP dependent enzyme that causes the loss of a carbonyl that is replaced by an amine. Majority of anti-bactericidals were discovered using the method of isolating natural products. Moreover, the drug of interest for Dr. Aldrich was Amiclenomycin, a Bio A in activator that inhibits the synthetic mechanism for biotin. The inhibition mechanism is powered by ketolysis that produces reactive species. 

Dr. Michael Huggins

On November 22nd I attended a seminar hosted by Dr. Michael Huggins on "hydrogen bonding studies with simple pyrrole derivatives". The seminar was an interesting insight into the work that Dr. Michael Huggins has carried out in his lab and how chemistry research generally takes place and the lengthy procedures it involves. Dr. Huggins described how he is very interested in supramolecular chemistry "chemistry beyond the molecule". The seminar was focused around the molecule dipyrrinone, and during the seminar he Dr. Huggins discussed many reactions which he has achieved and those which he wished to achieve and was experimenting with.
The part of the talk I found most interesting was the focus on hydrogen bonding, as this was something I could relate to and apply to the class. Much of the other parts of the seminar was difficult to comprehend as it was advance chemistry, however I could understand the hydrogen bonding present in the dipyrrinone which influences its shape. This occurred between the nitrogen and hydrogen molecules.
Dr. Huggins presented his findings on his attempts to synthesis a dipyrrinone amide, pyrrole sulphonamide and also discussed his use of analysis techniques that determine where the atoms are in a molecule in relation to space.
It is difficult to go into more detail about the seminar as I found it difficult to understand, however, I did learn a lot about the techniques, patience and persistence needed in obtaining results and making new discoveries.

Seminar w/ Dr. Courtney Aldrich

On Wednesday November 15th I attended the chemistry seminar of Dr. Aldrich. The title of the seminar was "Design of Antibiotics that Target Biotin Metabolism" and his goal was hopefully using it to treat TB. Dr. Aldrich is a professor at the University of Minnesota and is a researcher in the the department of medicinal chemistry. The first part of the seminar was discussing antibiotics; how they work, the development of them, and how in the past many have been overused. He later went on to talk about Tuberculosis and how many strains have become antibiotic resistant and pose a real threat to even the most developed countries, in terms of medical research. Up until this point I was following along quite nicely and comprehended a great amount on the subject matter. I myself am a Biology Major and am taking Microbiology this semester, so a lot of this tied in nicely. The second half of the seminar is where he lost me. He began to talk mechanisms and real chemistry. He made several jokes and the chemistry department (professors and grad students) laughed along, but I just wanted to return to the biology portion of the seminar. Based upon the graphs he showed his tests are showing promise, but much research is needed.

Design of Antibiotics that Target Biotin Metabolism

 On November 15, there was a seminar about "Design of antibiotics that Target Biotin Metabolism" by Dr. Courtney Aldrich from University of Minnesota. His seminar was focused on the synthesis of new antibiotics for tuberculosis. He started the seminar by introducing how little interest he had in science in his college years; He couldn't find what he really wanted to study, so he had to change his major five times before he finally knew what he really wanted to study. He joked about if he had little more interested in science early back then, he should've got a basic idea of majoring in chemistry because his last name is Aldrich.
He talked about history of antibiotics and importance of it. Before 1930, you could die because there weren't many antibiotics. 1946-1960 was the golden age of antibiotics. But there isn't any new antibiotics after 1987, therefore, Dr. Aldrich is trying to design new antibiotics. He said there are two major strategies and challenges in antibacterial drug industry: Unbias-phenotypic whole-cell screening and biased-target-based rationale design. He is more focused on biased-target based rationale design. He mentioned the cofactor biosynthesis as drug target and explain the essential in a variety of biological processes and its selective to microorganisms.
He, then, talked about Tubercuosis. Tuberculosis is cased by Mycobacterium tuberculosis, transmitted by soughing and sneezing, and leading cause of bacterial infectious disease mortality with 1.4 million death per year. I was very surprised when I heard this fact. He also showed synthesis of Tuberculosis, Amiclenomyclin(ACM), and aromatizoction inhibitor, and talked about different method testing and making antibiotics. However, I was only able to understand very few concept such as stability, pKa, configuration, basic synthesis that we learned in class, etc.
At the end, he summarized his seminar by three points: impact of BirA Expression Levels on Drug susceptibility by Dir Schanappinger, unpublished result: Target-based approaches have merit, but most have in vivo genetic validation: use of conditional mutants in certain situation. It was very great opportunity that I get to hear his seminar and talk to him in person, because I also want to be in chemistry research industry. He was very knowledgeable and very passionate of chemistry industrial. I learned more than I expected and willing to join more chemistry seminars next time. 

The Potential of Silymarin

Dr. Stephen J. Polyak's lecture on 8 November was on the potential medical benefits of Silymarin, which comes from the seeds of the milk thistle plant. Silymarin is commonly known as milk thistle and was used in Greece and is continued to be used for treatment of hepatic gallbladder diseases and to protect again liver deterioration from ingested toxins.

It has the potential to modulate metabolism inflammation and immune response. It has and is continued to be consumed by liver disease patients and HIV patients for its hepatoprotective properties. Noteworthy was when Dr. Polyak mentioned that there is no effect on liver enzymes and HCV in vivo using oral dosing of silymarin. Silymarin is alluring to researchers for its display of multiple effects including blocking:

• Hepatitis C virus
• NF-kB activation (anti-inflammatory properties)
• Virus induced stress
• T cell proliferation
• Cytokine production
• HIV virus

Dr. Polyak also mentioned how his team uses Ingenuity Pathway Analysis (IPA) which is a web tool used to analyze data and overlay experimental data to draw associations and generate more accurate hypothesis. IPA helps to identify the most relevant signaling and metabolic pathways and biological functions for a particular set of genes. It also predicts the downstream effects of diseases as well as activation and inhibition factors. Comparing affected phenotypes becomes much easier. Hopefully more funding will come to Dr. Polyak and his team so they can get down to the specifics of how exactly silymarin affects the body.

Seminar with Dr. Courtney Aldrich

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.

Hyrdogen Bonding Studies with Simple Pyrrole Derivatives

Last week I attended Dr. Michael T. Higgins'  seminar "Hydrogen Bonding Studies with Simple Pyrrole Derivatives." Dr. Michael T. Higgins works at the University of West Florida and obtained his Phd at University of Nevada - Reno.

Dr. Higgins' overall focus is supramolecular chemistry, which he defined as "chemistry beyond the molecule." It is centered around the study of molecular systems whose most important feature is the components of the systems that are held together by non-covalent bonds. Basically in his words, it supramolecular chemistry focuses on the idea that you "have a product, so what are you  going to do with it?"

The focus of the seminar was on making pyrrole derivatives. The base of these reactions is the dipyrrinone molecule, which loves to self associate. However, in his work, Dr. Higgins wants to build a host and invite guests (anions) to come in and make a bond, meaning he wants to add different substances to the dipyrrinone molecule (see image below). This is done by disrupting the dimerization (self association) and push it towards forming new bonds. In the dipyrrinone molecule, the carbonyl ion is important because it is electronegative, thus repulsing atoms.


A bulk of the seminar focused on dipyrrinone amides, where Dr. Higgins wanted to add amides to the dipyrrinone. Dr. Higgins tried different ways to make this reaction happen. First he tried by making the parol with the amide in place. However, this method did not work. Now he is trying to make this reaction occur via a short synthesis of amides from a-keroacids. Lastly he addressed a revisited synthesis, which is still in progress, but he is able to make the dipyrrinone amides.

Dr. Higgins also touched on pyrrole sulfonamides and organophosphates, particularly sarin. While talking about organophosphates, he mentioned they are trying to develop a system to detect them via an optical response. If an organophosphate is present, it will go through a chemical reaction and become florescent, thus indicating it is there.


References:

Higgins, M. Molecular recognition studies with dipyrrinone derivatives. University of West Florida Department of Chemistry. November 30, 2013, from http://uwf.edu/chemistry/facstaff/huggins/research.cfm.

Dr. Michael Huggins' Hydrogen Bonding Studies with Simple Pyrrole Derivatives

Recently, I have attended Dr. Michael Huggins’ from West Florida presentation on Hydrogen Bonding Studies with Simple Pyrrole Derivates. His studies were very complex at an advance level that was hard to comprehend completely. However, I was glad that he is an organic chemist, so some vocabulary were familiar.

He was very interested in the reaction of Dipyrrinone structure because of its rich environment for hydrogen bonding. It has hydrogen-bond pocket that could establish this possibility. The structure is a polar functional group and non-polar ends. It loves to self-associate. Many of Dr. Huggins’ experiments resulted in a failure. He presented many data on different synthesis that his students have worked on.

There was a new synthesis of Dipyrrinone, which incorporated amide. This attempt failed because it could not bond to another compound even when tried with heat. He stated that there was a revised synthesis and it did work, but he didn’t specify it clearly enough for me to gather the data from him.

He mentioned that sulfonamides were created from Sodium metal in ice bath, which created the product pyrrolon. There were other methods that he used including sulfuric acid and water by adding RNH2/Et3N together and get the final sulfamides. I was confused with this compound because he assumed that everyone in the room knew about the compound, so he did not explain any properties or how it created sulfamides.

It was interesting to see how he used a wide variety of methods and compounds to test for the hypothesized product, but many tries failed. Dr. Huggins said he will continue to come up with more different ideas that could work with hydrogen bonding in sulfamides and used Dipyrrinones to create larger structures with a linker in the future.  

Dr. Michael T. Huggins

“Hydrogen Bonding Studies with Simple Pyrrole Derivatives”

-  Dr. Michael T. Huggins

Dr. Huggins spent his time talking about his work with the Dipyrrinone structure.  The majority of the talk was rather in depth so I took notes on what I could.  It seemed that most things that Dr. Huggins and his staff did to try and get the Dipyrrinone to react the way they wanted ended up failing.  They tried using amide groups but after many different methods and failures he stated that he is just “sick of amides.”  Another problem for his research has to do with the environment of Florida.  The humidity has a major effect on the yield that he is able to produce in the lab, which has a wide range of anywhere between 30-80% of starting material.  The thing that I found most interesting was the fact that he wants to use fluorescent Dipyrrinones to help in the detection of certain organophosphates.  These detectable chemicals could be harmful ones such as herbicides, or nerve gas.  If you wanted to test the runoff from a farmer’s field then by using UV spectra and the fluorescent Dipyrrinones you can determine if the water is in fact contaminated.  He also mentioned that the chemical agent Sarin could be detected as well such as the gas that was used in the Syrian attacks.  The test would essentially turn the color from the oximate color which could be purple to the yellow green color of the oxime, which would confirm the presence of that particular chemical.  This to me seems like it has so many different useful applications.  To sum up the lecture he spoke briefly about Pensacola and the University of West Florida.  Pensacola is the oldest city in the US, predating both St. Augustine and Jamestown.  The school has 13,000 students who go there.  

 

 

Dr. Aldrich

Dr. Aldrich gave a presentation on November 15 about designing antibiotics for tuberculosis that target biotin metabolism. He began by giving a history  of antibiotics and talked about the importance of biotin in the TB bacterium. Biotin is a cofactor that is needed to synthesis the fatty acid portion of the bacteria's cell envelope. Without a cell envelope, the bacteria is susceptible to the harsh conditions of the outside environment, including antibiotics and other drugs that could destroy the bacteria. Dr. Aldrich talked about tests that could be done when testing the antibiotics and different approaches to take when making the drugs. When designing an antibiotic there are many obstacles to over come - creating a molecule then finding out that it is unstable and is gone the next day, difficulty in stabilizing the compound, specificity of the compound, etc. 

He talked in great deal about all the time and work and research that goes in to this kind of thing. The entire time the presentation was going on, however, I could only think about one thing: how much the antibiotic will cost. Over 95% of TB deaths occur in poor countries. Most of the people in need of medications are poor and can’t afford treatment, so they die. Why make an antibiotic for a disease that majorly affects poverty-stricken individuals and seriously poor countries when they won’t be able to afford it? Whenever they find these new antibiotics, I hope they work to make them affordable so that the drug can do what it was made to do, save lives.

Dr. Huggins - Dipyrrinone

         Dr. Huggins gave a seminar on November 22 on the main topic of Dipyrrinones. This was his main subject since he works with undergrads at the University of West Florida on Dipyrrinones. From what I could gather, his goal with the undergrads is to be able to synthesize Dipyrrinones and interrupt their stability, primarily through the use of amides. However, listening to Dr. Huggins, it was very clear that amides are a pain in the neck to work with. One student offered an alternative to amides, but Dr. Huggins stated that the goal is mass production of Dipyrrinones for undergrads, and that while other compounds would certainly work, they were too costly.  In his studies, a synthesis of Dipyrrinone was found  to be possible with amides in one way, but it was still a very messy process.
         The reason for the failure of multiple Dipyrrinone syntheses inlcuded self-association, because Dipyrrinone tends to bond with itself. However, KOH and CH3OH can form 88% Dipyrrinone that has a planar confirmation. Also, Dipyrrinone has very strong hydrogen bonds, so steric interactions are required to interrupt self-association. Amides yielded horrible results in percentage Dipyrrinone formed if at any was formed at all. Pyrole Sulfonamide also yielded horrible results, particularly due to the humidity of Florida since immediate dryness is required in end procedure for decent results. Amides also failed in adjusting solubility in Bis-Dypirrinones since trans amidation happens immediately in the reaction process.
          While Dr. Huggins never got the result he purposefully tried to accomplish, he was able to form helpful compounds by accident in the process. The chemicals made in this process are all highly fluorescent, so thankfully the Dipyrrinone research is useful in other ways than intended.

Dr. Michael Huggins

I attended Dr. Huggin's seminar on November 22. It  was very fascinating and he was very engaging. Considering that 95% of everything he talked about completely went over my head. It was some very intense chemistry, the only thing that made sense to me was Hydrogen Bonding. After looking over my notes and doing a little research, the seminar made more sense.

His research and main subject for the seminar was Dipyrrinones. These molecules tend to want to react with themselves. His research is geared toward forming different reactions with this molecule.



According to Dr. Huggins intruducing the guest into this equation was very difficult. Most of his attempts failed. He also stressed his dislike for amides, due to them rejecting his experiment.

He also tried adding sulfonamide, from the results he shared, it seems as if the sulfonoamide was working much better than the first experiment.

Dr. Courtney Aldrich : Design of Antibiotics that Target Biotin Metabolism

Dr. Courtney Aldrich seminar was on antibiotic design, specifically about those that target Biotin metabolism which is utilized by Mycobacterium tuberculosis, the organisms responsible for the disease, tuberculosis. According to Dr. Aldrich, new antibiotics will be developed through the use of the unbiased phenotypic whole-cell screening technique in which compounds with antibiotic activity are obtained and of those, the ones that are multi-target inhibitors are identified.

According to Wanisa Salaemae, Al Azhar, Grant W. Booker, Steven W. Polyak, School of Molecular and Biomedical Sciences, University of Adelaide, South Australia 5005, Australia, Biotin is an important micronutrient that serves as an essential enzyme cofactor. Bacteria obtain biotin either through de novo synthesis or by active uptake from exogenous sources. Mycobacteria are unusual amongst bacteria in that their primary source of biotin is through de novo synthesis.

Tuberculosis has been classified as a “modern emerging infectious disease” because though we are very familiar with the standard and older forms of the disease, we are much less familiar with the newer, drug resistant and fungal forms of the disease. Dr. Aldrich was able to describe the ways antibiotics are designed and created. These are in two ways; biased based target  where researchers focus on specific enzymes' pathway or phenotype whole cell screening which would be the method which the majority of future antibiotics would be discovered... 

The complex life cycle of mycobacterium tuberculosis, the pathogenic bacilli responsible for TB, also contributes to the bacteria’s extraordinary ability to evade antibiotic therapy (Russell et al., 2010). Most antibiotics are effective against actively growing Mycobacterium as they target metabolic processes required for the primary progressive stage of infection (Baek et al., 2011; Koulet al., 2011).

Dr. Aldrich concluded that the new biotin-targeted drugs development can be effective as a product of biased-target based rationale and that it is very important to recognize the drug’s use in vivo in the body-for the drugs he has been working to synthesize as well as all other drugs.

Silymarin may be the key...

I attended the seminar by Dr. Stephen Polyak on the study of silymarin. Silymarin is an extract from the seeds of the milk thistle plant and contains aspirin and caffeine. It's derived from ancient European medicine practices and was shown to prevent liver disease in experimental animal models. It acts primarily on the cells to elicits multiple cytoprotective effects. Cytoprotection is when chemical compounds provide protection to cells against harmful agents. (http://www.ncbi.nlm.nih.gov/m/pubmed/1791051)

Silymarin is widely consumed by people with chronic HCV or HIV. Some of the cytoprotective effects include blocking hepatitis C virus, inhibiting cellular pathways, blocking virus-induced oxidative stress, and by blocking t-cell proliferation and pro-inflammatory cytokines production. Silymarin and silybins also rapidly induce various cellular stress responses resembling energy and nutrients stress.Scientist use IPA to collect, test and interpret biological data. Ingenuity Pathway Analysis (IPA) is a web-based functional analysis tool for comprehensive omic data. The IPA steps include generating data, performing basic statistics, using query ingenuity knowledge base, analyze affected biology, and analyze visual data in context. (http://norris.usc.libguides.com/IPA) Silymarin may ultimately prevent liver diseases and primary liver cancer.

Dr. Courtney Aldrich

Dr. Courtney Aldrich’s lecture was based on the design of antibiotics that target biotin metabolism. Dr. Aldrich is an associate professor in the Center for Drug Design at the University of Minnesota. He also got his PhD from the University of Minnesota. Dr. Aldrich is working on the synthesis of a new antibiotic for patients with tuberculosis. The first antibiotics were developed in the early 1330’s, in Germany. The introduction of antibiotics increased the average life span by 25 years. The last antibiotic was introduced in 1987. Scientists have not created new antibiotics since then, thus making this period “the discovery void.” There are two popular ways to create antibiotics: phenotypic whole cell screening and biased-target based rationale. Tuberculosis is an old disease but there are newer and more drug resistant forms of the disease. The goal of Dr. Aldrich’s research is to inhibit the biotin pathway so that the bacterium is not able to replicate and multiply inside of the host cell. Dr. Aldrich and his team believe that if they target specific Bio enzyme A in the biotin pathway that will serve as a road block to tuberculosis. Dr. Aldrich’s research is very complex and time consuming; hopefully he will succeed in his research and come up with an antibiotic for tuberculosis.


 
http://www.cdd.umn.edu/Members/ExternalMembers/index.htm

 

Seminar

The professor from the University of West Florida visited UNCG. He made a speech on his work about Pyrrole Derivatives and the hydrogen bonds. He talks about how they are doing a study in Pyrrole Derivatives. He has been working to figure or to workout what he could with this dipyrrinone structure for seven years. He works with his undergraduate students and they put in a lot of work in from what I've seen. He used NOE spectrometry, NMR's and mentioned how the reactant they had is not going to work with a bulky group. He said the bulky group causes steric hindrance; this was what we learned in class. He showed us all a picture of what worked when they added an amide group to the dipyrrinone but he also showed the one that they failed on. Near the end, he showed pictures of compounds that were florescent. There were different colored ones because the compounds react accordingly to the substances added. His speech was interesting. I am glad I know more of what he's talking about due to class lectures!

Dr. Courtney Aldrich - Design of Antibiotics That Target Biotin Metabolism

Hello to my fellow CH351 students (and Dr. Petersen),

Unable to attend the beer brewing lecture earlier in the month, my schedule decided (for me) that I was going to attend the 15 November lecture. Fortunately for me, Dr. Courtney Aldrich was giving the lecture! Dr. Aldrich (related to NBA player Cole Aldrich?? Sorry, didn't ask him) works at the University of Minnesota as an associate professor in the Center for Drug Design.

One thing that stuck out to me from his lecture was that he had five majors before deciding that he wanted to be a chemistry major. He knew he was in the right field when he took his first class of Organic Chemistry, which obviously must have been taught by someone like Dr. Petersen.

Prior to antibiotics, people often died when they came down with a virus. Since antibiotics were introduced in 1935, the average life span has increased by 25 years! 1945-1961 was known as the Golden Age of Antibiotics, as a plethora of antibiotics were being discovered. But the last antibiotic that was discovered occurred in 1987. Since then, no new antibiotics have been found. Dr. Aldrich is seeking ways to change that through his research with the biotin metabolism. There are three strategies for discovering new antibiotics, which Dr. Aldrich believes should all be continued to be used. The one strategy that he is using with biotin is the cofactor biosynthesis as drug targets. As he went through his lecture and showed the incredibly complex molecules he was using, I would catch a glimpse of something that I learned in class, such as stereochemistry or cis/trans isomers, and try to understand where he was going.

Dr. Aldrich was extremely knowledgeable about the subject of antibiotics and how chemistry plays a role in their discovery and development. I am fascinated by people who are subject matter experts in any field. I recently watched Somm, a documentary about nerdy wine lovers. I don't know anything about wine, but their intense devotion to what they were studying was captivating. Listening to Dr. Aldrich speak about something that he has devoted his life to was very humbling. I am extremely happy that we have people like him working to find cures for diseases and improving the quality of everyone's lives.

Go Chemistry!

Design of Antibiotics that Target Biotin Metabolism

The seminar I attended earlier this month gave me some really interested insight into how organic chemistry provides the basis for the art of chemically engineering medicine to target biotin metabolism. The guest Speaker, Dr. Courtney Aldrich received his PhD from the University of Minnesota and had the privilege of working overseas in Germany on a joint venture between the US and Germany. Dr. Aldrich’s focus or main contributions to medicinal science are in the synthesis of new antibiotics for tuberculosis.

            Before hopping directly into his material Dr. Aldrich briefly discussed the mechanistic origins of antibiotics. He showed us a very fascinating chart on the different types of antibiotics and to much dismay pointed out that there is still today a lull in the discovery era of antibiotics. The last antibiotic had been discovered back in 1987 over twenty years ago. This lapse in antibiotic discovery is known as the “discovery void”. Dr. Aldrich then went on to explain how antibiotics were mechanistically designed and created. The two distinct ways antibiotics are developed are biased-target based in which researchers focus on specific enzymes in the pathway or phenotype whole-cell screening which he explained would be the method by which the majority of future antibiotics would be discovered. Much of Dr. Aldrich’s research has been based on the first of these two methods. Dr. Aldrich strongly believes that targeting specific Bio enzyme A in the biotin pathway will some how provide that road block to tuberculosis. This would most certainly be an astonishing feat and i really feel honored to be able to get a glimpse into a future scientific breakthrough.