Kelin Brace, Biochemistry and Molecular Biology
“Synthesis of C-nucleosides and Their Biological Implications”
Modified nucleosides have been intensely studied for their ability to alter normal biological functioning, and are increasingly being considered as important medicinal candidates. In particular, the deazapurines have been investigated because of their antimicrobial, antiviral, and anticancer potential. These particular analogues show promise because their structure is similar to that of the natural nucleosides, and their carbon-carbon glycosidic bond is impervious to hydrolytic and enzymatic cleavage, which is a serious problem for many nucleoside drugs. A number of C-7 substituted pyrrolo[3,2-d]pyrimidines (also known as 9-deazapurines) have also shown inhibitory activity against purine nucleoside phosphorylase (PNP), an enzyme that is known to destroy many nucleoside drugs before they can reach their target. This finding is significant because this suggests these compounds could then be co-administered with nucleoside drugs, thereby blocking PNP and allowing the drug to carry out its therapeutic duties. The focus of this investigation will be to synthesize several 9-deazapurine analogues as potential inhibitors of PNP. Their synthesis will be accomplished through the use of various carbon-carbon organometallic coupling reactions and other functional group transformations. Once the compounds are synthesized and characterized, their medicinal properties will be assessed through the use of biological screening to be carried out by our research group's collaborators. The results of this study will provide new insight into the biological importance for the 9-deazapurine scaffold as potential drug candidates.
When and how did you find out that you could do independent research work as a UMBC undergraduate?
Before coming to UMBC, I had heard on several different occasions that undergraduate research was very big on campus. As a Meyerhoff scholar, I was encouraged to find a mentor and carry out my own research.
How did you find a mentor and decide on a project? How did you know this was the project you wanted to do?
I had one of my teachers my as a mentor, and I requested to work with her because I enjoyed her in class and found her research interesting. We chose a project for me that would fit well into the lab's current work while still giving me enough independence to work on my own.
How much time will you put into this research work?
Over the summer I am working around 30 hours a week on my project, and during the school year around 10-15 hours per week.
What academic background did you have before you started on this research?
Before starting my research I had taken the chemistry classes needed to have a basic understanding of our research. However, in my more advanced courses I am constantly learning things that apply to the research I am doing now.
How did you learn about applying for the Undergraduate Research Award? Was the application hard? Did your mentor help you?
My mentor suggested I apply for the URA. The application was not difficult, but my mentor did help me condense the scope of the whole project to the short application.
What is your advice to other students about getting involved in research?
The teachers at UMBC are very passionate about their research. If you are honestly interested in what they are doing, most people will be very happy to talk to you and maybe even let you join their lab.
What are your career goals?
I would like to pursue an MD/PhD degree upon graduation.