Pyrrole- and imidazole polyamides are analogs of distamycin. They can be designed totarget and bind in the minor groove of any DNA sequence. In this study, two polyamides that bind 5'-ACGCGT-3' were designed: one is f-IPI  which binds as a side-by-side, antiparallel stacked dimer. The other is f-IPI2  , which is a covalently linked H-pin dimer of f-IPI  . The two f-IPI  units are joined at the N1-position of the two corresponding pyrriole units through an ethyleneglycol linker. 5'-ACGCGT-3' is the MluI cell cycle box (MCB), which is a transcriptiona; factor binding site that activates the expression of the HuCdc7/Dbf4 core gene in mammalian cells. Dbf4 is the regulatory subunit of Cdc7 kinase, which is essential for the initiation of DNA replication throughout S-phase. In this study, the DNA binding properties of f-IPI  and f-IPI2  will be presented as well as their ability to affect the expression of the Dbf4 gene in human cells. The effects of these polyamides on cell growth and apopotosis of cancer cells in culture will also be presented.

Control of the human DBf4 gene by a small pyrrole and imidazole-containing polyamide (f-IPI ) andnot its H-pin analog (f-IPI<sup>2</sup> )

245th National Meeting (2013)

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Control of the human DBf4 gene by a small pyrrole and imidazole-containing polyamide (f-IPI ) andnot its H-pin analog (f-IPI2 )

Control of the human DBf4 gene by a small pyrrole and imidazole-containing polyamide (f-IPI ) andnot its H-pin analog (f-IPI² )