Biochemical and Biological Properties of Fluorescent Polyamides

Faculty Mentor(s)

Dr. Balaji Babu, Hope College
Dr. Kimberly Brien, Hope College
Dr. Vijay Satam, Hope College
Dr. Shicai Lin, UCL Cancer Institute
Dr. Konstantinos Kiakos, UCL Cancer Institute
Dr. John A. Harley,UCL Cancer Institute
Dr. Moses Lee, Hope College

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Polyamides containing imidazole and pyrrole units target the minor groove of DNA by making specific sequence specific interactions and hydrogen bonds with the four base pairs of DNA in stacked, anti-parallel dimers. Other groups, such as phenyl and formyl, have been added to these polyamides with the goal of increasing sequence specificity, binding affinity, solubility, as well as to enhance the convenience in synthesis. However, in order to track the movement and localization of these compounds in cells, the need for polyamides that both fluoresce and bind to DNA in a sequence selective manner was realized. Ligands (Hx) of Hoechst 33258 (bisbenzimidazole), a small fluorescent molecule that acts like two consecutive pyrroles in targeting A/T rich sequences of DNA, were incorporated into polyamides. One such polyamide, Hx-IP was found to bind a sequence 5’-TACGAT-’3 present in the 5-flank of the ICB2 element in the promoter of topoisomerase II, thus blocking the repressor transcriptional factor NF-Y. A variety of DNA binding studies have been conducted on Hx-IP. Results from these studies will be presented

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