Nathaniel Kim, Chemistry
"Size Extended Pyrimidine Nucleosides: A Fundamental Study of DNA Structure and Stability"
Faculty Mentor: Dr. Katherine Seley-Radtke
Expected Graduation Date: May 2011
Deoxyribonucleic acid (DNA) is the genetic blueprint for all living organisms. Structurally, DNA consists of two polymeric chains of nucleotides, anti-parallel to each other forming a double helix. Intermolecular hydrogen bonding across the helix, stacking interactions, and the width of the helix are some of the important features of DNA crucial for its stability. In order to investigate these requirements of DNA, we have designed and synthesized size-extended pyrimidine nucleosides. These thymidine and cytosine analogues have a heterocyclic spacer ring, which results in displacement of the pyrimidine ring away from the deoxy-ribose and is expected to increase the width of the double helices. Since the hydrogen bonding units are intact these unnatural nucleosides will afford base pairing similar to thymidine and cytosine. Presence of an additional hetero-aromatic ring should enhance stacking of these nucleosides within the helix, thus providing greater stability than the natural nucleosides as well as to provide additional hydrogen bonding interactions. The biophysical effect of the unnatural nucleosides will be evaluated by incorporating them into oligonucleotides and monitoring their melting temperatures.