Tye Seideman

Summary of the MIDD research assistantship

1. Synthesize ten or more tryprostatin analogs

A key step in our synthesis (coupling C2 alkylated gramine salts with diketopiperazine) has been significantly more challenging to reproduce than was expected. I am hopeful that I will soon have this coupling reaction mastered, allowing me to synthesize new analogs much faster.

2. Evaluate potential for tryprostatin analogs as BCRP inhibitors

Based on literature and preliminary docking studies performed. There is potential for developing tryprostatin into an effective BCRP inhibitor. This will potentially lead to a tryprostatin based drug to be used as a cocktail drug for drug resistant cancers. Additionally, this could lead to a tryprostatin drug prescribed as a single or main chemotherapeutic that is effective against drug resistant-cancers.

3. Evaluate potential for tryprostatin as an Alzheimer’s disease treatment through interaction with Tau

I have had preliminary talks with Nick Silvaggi about co-crystallization studies for TPS A with tubulin, Tau, or BCRP. Tubulin may be difficult as it is a filamentous protein, but TPS A‘s microtubule polymerization inhibition may reduce or remove this obstacle. BCRP is a membrane protein which tend to be difficult to isolate and crystallize while maintaining its structure. Once I have made significant progress in the synthesis of TPS A, I plan on having further talks with Dr.  Silvaggi. Identifying TPS’s exact mode of action is essential for evaluating its use as an Alzheimer’s treatment.

Undergraduate Student: Grace Geiger 

Over the course of this past year, I’ve had the opportunity to work in Dr. Hossain’s laboratory under the direction of Tye Seideman. From this experience, I’ve developed a skillset that will enable me to confidently work in biochemical laboratories once I graduate. I have been involved in research for the majority of my undergraduate but working with Tye gave me insight to how drug compounds are conceptualized, synthesized, and analyzed. I learned how to perform column chromatography, thin layer chromatography, and prep thin layer chromatography. Tye taught me how to properly analyze compounds using proton nuclear magnetic resonance and mass spectroscopy. I learned how to prepare samples for analysis and was eventually authorized to use the 500 MHz NMR independently in the Summer of 2022. In addition to purification and compound analysis, I performed several organic synthesis reactions. Under Tye’s close supervision, I completed, amide couplings, hydrogenations, reductive animations, and cyclization reactions. This was all completed to synthesize diketopiperazine compounds that would be used in a later series of reactions Tye had planned. I am extremely fortunate to have had Tye as my mentor this past year. He is an excellent teacher, and has a way of tying real world examples into every task we completed. When I made mistakes, Tye utilized it as a learning experience and his encouragement gave me the confidence to try again. This past year has provided me with invaluable experience that will no doubt enable me to succeed in my future endeavors.

Undergraduate Student: Ameer Eweisi

I had the opportunity to work in Dr. Hossain’s laboratory at UWM with Tye Seidman over the past 4 months. During the research I learned a lot about being an organic chemist, and learned many techniques associated with organic chemistry research. However, I didn’t learn by myself, so I am very grateful that I worked with Tye who had a big experience about doing research and working as a chemist. Not only he had some good experience, he also was very friendly and always urged to help me and teach me. Tye was very easy to understand and he always made my research time enjoyable as he always asked good questions that made me think about the experiment we are doing and understand it. Also, he always made sure that I have hands-on experience which made me not only learn how things are done but also how to perform things. My role in this research is to help in synthesizing compounds by carrying out reactions and purifying products to produce the maximum yield possible.

To be more specific, I prepared and carried out many types of reactions such as reductive amination using sodium triacetoxyborohydride, and testing sodium borohydride. Another reaction I did was applying Boc protections on compounds. During the research I carried out some analysis such as prep TLC, analytical TLC, NMR, as well as mass spectroscopy. I also carried out purification techniques that includes running a column, prep TLC and crystallization. All of these things that I have done were beneficial in my learning process. From every step I made and every mistake I did I always learned from it. I learned from it because I always had feedback from Tye so that he always told me what I did wrong and what is the right thing to do. He also told me how I could have avoided my mistake which made me recognize my mistake and learn from it so that it would never be repeated. I also learned how to better organize the steps needed for a reaction that made me do a reaction faster, safer, and get as much yield of the product as I could.

In conclusion, I learned a lot in this research by carrying out different reactions, and by analyzing and purifying many compounds by using different methods. This was also done with the help of the whole research group in general under the administration of Doctor Hossain by giving us feedback along the semester, but more specifically because of the help of Tye, who always guided me throughout my research.