Nathaniel Kim, Chemistry and Political Science
Tricyclic Carbonucleosides as Medicinal Agents for HCV Polymerase
Faculty Mentor: Dr. Katherine Seley-Radtke
One of the major public health risks in the world today is the Hepatitis C Virus (HCV). The current standard therapy for HCV infection, co-treatment with interferon-a-2b and ribavirin, has shown low efficacy and side effects, pointing to the need for new and more efficacious treatments. In order to develop novel candidates against HCV that exhibit greater inhibition than current treatments while minimizing cytotoxicity and side effects, we have designed and synthesized a series of tricyclic nucleoside analogues that have strategically designed features that should prove highly beneficial. These tricyclic purines nucleosides feature a carbocylic ring in place of the ribose moiety. This structural modification increases both the nucleoside’s stability towards cellular repair enzymes and its ability to cross membranes, both of which are problems associated with ribose analogues. A second modification has been incorporated into the tricyclic base; replacement of the N-7 nitrogen provides a 7-deaza pyrrole moiety. A number of 7-deaza compounds have been shown to be potent inhibitors of HCV while maintaining low cytoxicity. Thus, combining these two structural attributes with that of known tricyclic nucleoside HCV inhibitors should synergistically result in increased anti-HCV activity.
How did you find your mentor for this project?
I e-mailed professors whose research interested me. Dr. Seley invited me into her lab as an undergraduate researcher. I have worked with her on research since the start of sophomore year.
How did you know this was the project you wanted to do?
I learned during a summer internship at NIDDK/NIH that synthetic chemistry was something I might want to pursue. My research in the Seley lab is, now, primarily synthetic chemistry.
Do you get course credit for this work?
I got three credits for CHEM 499 for the fall and spring semester.
How much time do you put into it?
I spend about 15 hours in the lab every week. With any type of research, and even more so with undergraduate research, the research project goes as far as the time you're willing to put into it. Plus, I enjoy being in the lab and doing what I do.
You have a $1,500 Undergraduate Research Award from UMBC for your work. How did you hear about this program?
Dr. Seley and a couple of my friends who previously won a URA encouraged me to apply.
Was the application difficult to do?
The application itself was a good experience to go through. It helped me to fine tune my thoughts and proposals on a possible research topic in a coherent manner. This ability becomes very important if you go on to further research, especially when you're applying for other scholarships and research grants.
How much did your mentor help you with this?
My mentor facilitated my research, the research project I worked on, and made sure I was not overwhelmed. The research itself is primarily my own.
What is your advice to other students about getting involved in research?
You can't get into a research group as an undergraduate if professors don't know who you are. If you're at all interested in conducting research, find what research topics might interest you and e-mail professors who you feel fit you best.
What has been the hardest part about your research?
Time management. I have a lot of other responsibilities as a Desk Staffer and SGA member. Being able to balance my time is something I've had to learn.
What was the most unexpected thing?
Everyone will hit the preverbial wall when they conduct research, where everything seems to come to a screeching halt. This wasn't unexpected but it was something that I had to push through and stay dedicated to.
How does your research relate to your work in other classes?
I've used several techniques from Organic Lab and Biochemistry and built upon other research techniques that I already knew. You're not expected to know everything when you enter a research group, but it's good to know the basics.