Methylated DNA binding (MBD) proteins control transcriptional regulation by binding methylated DNA to modulate transcriptional activation and silencing of specific genes such as tumor suppressors. The goal is to explore the structure/function relationship between MBD proteins and methylated DNA recognition. By synthesizing the methylated DNA binding region of the MBD1 protein, binding studies test the peptide’s affinity and specificity for methylated DNA. Fluorescence and circular dichroism techniques are utilized to determine the binding affinities and structures of peptides. Studies of peptide mutations can monitor the effectiveness of methylated DNA binding compared to the original peptide. The most structured peptide is expected to have the highest affinity and selectivity, leading to a peptide which can compete with the MBD1 protein for methylated DNA binding. This research could produce a series of peptides which can inhibit methylated DNA binding domains and reduce the silencing of tumor suppressor proteins, providing effective cancer therapeutics.

Redesigning proteins to specifically bind methylated DNA and inhibit methyl-CpG binding proteins for transcriptional regulation

251st National Meeting (2016)

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