Interaction between Oligonucleotides and Biscarbazole Derivatives
Mentor:THOMAS MINEHAN, Associate Professor of Chemistry, California State University of Northridge
In this study, we compared the binding affinity of biscarbazole derivatives A and B for oligonucleotides. The purpose of this study is to identify the structural characteristics of compounds that have a specific binding affinity for nucleic acids. The interaction between DNA and biscarbazole compounds was analysed using UV and Fluorescence spectroscopy. Drugs with high affinity for DNA should have binding constants (Kb) of >10^5 L/mol. Our work demonstrated that biscarbazole derivatives A and B have a significant binding affinity of magnitude >10^7 L/mol. Based on UV spectroscopy analysis, bathochromic and hypochromic shifts demonstrated intercalative properties of the modified biscarbazole A and B compounds. However, the original fluorophore, biscarbazole, did not exhibit any significant hypochromic or bathochromic shifts. This study presents three key features of biscarbazole fluorophore: its intense fluorescence, tightness of binding higher than a known intercalator, ethidium bromide (Kb= 10^4 - 10^6 L/mol), and its potential to be modified for binding to specific DNA base pairs. Most known DNA intercalators are either major or minor groove binders. However, the two aromatic nitrogens at the opposite sides of biscarbazole compound may be decorated with varied substituents that may bind to both minor and major groove of DNA helix. Targeting both grooves simultaneously may allow even greater DNA binding specificity. The binding specificity of biscarbazole compounds may be used to effectively target certain regions in a gene, such as promoters, enhancers, and silencers.