A Building Block Approach: A New Way of Thinking about Polyamides and Their Impact on DNA Sequence Recognition
Dr. Moses Lee; Dr. Kim Brien; Dr. Pravin Patil
Polyamides bind strongly to DNA sequences, including gene sequences involved in DNA replication and transcription of cancerous cells. The pyrrole and imidazole units in the polyamides bind to Adenine/Thymine and Guanine/Cytosine base pairs, respectively. Hx units, derived from Hoechst 33258 behave like two consecutive pyrrole units and bind A/T base pairs. The purpose of this study is to extend the DNA sequence recognition capability of Hx polyamides by incorporating the Hx unit close to the C-terminus end of the molecules. The goal in designing such “building block” Hx polyamides is to optimize the curvature and position of Hx with respect to sequence selectivity and binding affinity. The synthesis and DNA binding properties of two of such Hx polyamides will be described.
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