TITLE: Sequence Specific Targeting of DNA using Polyamides

SPEAKER: Professor Karen Buchmueller,

TIME: Thursday Mar. 30, 2006 at 4:00 PM

PLACE: George P. Williams, Jr. Lecture Hall, (Olin 101)

A wide variety of diseases, including cancer, can be treated at the genetic level through the development of compounds that target DNA. These compounds are used to disrupt the expression of deleterious proteins by inhibiting the binding of transcription factors that 'turn on' the gene. It is clear that there is a need to selectively target specific DNA sequences. The minor groove of DNA is the target for several classes of small molecules, including polyamides. Changes in the pyrrole and imidazole content of these polyamides allows for the alteration of sequence specificity. Several examples exist of polyamides that are able to inhibit transcription factors and subsequently regulate the expression of a specific protein. However, many polyamides have shown weak association to DNA and until recently there were no tools to predict the affinity of polyamides for their cognate sequences. The content and context of heterocyclic moieties, or language, within a polyamide is linked to its DNA affinity and partial deciphering of this polyamide language has already improved the design of the next generation of sequence selective polyamides. This presentation will focus on the thermodynamic and structural differences amongst related polyamides and how these differences correlate to the polyamide 'language'.

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