Towards the inhibition of the HMGA1 protein through selective inhibition of a single AT hook

PAC Gym

High Mobility Group A (HMGA) proteins are a family of proteins involved in the regulation of various transcription factors. HMGA proteins bind to DNA through two or three characteristic AT-hook motifs that bind cooperatively to AT rich regions of DNA. When found in adults at high concentrations, these proteins are commonly associated with metastatic cancer and often signify a poor prognosis. Our research has devised a system to selectively modify DNA to lessen the binding affinity of the protein to DNA by targeting a single AT hook. Azido modified DNA strands were created with non-natural nucleotides through the polymerase chain reaction. The DNA were further modified by the addition of a bulky group. It is postulated that the addition of this bulky group changes the structure of the DNA slightly, lessening the affinity of the entire protein for the DNA. Unmodified DNA and the click product were verified through gel electrophoresis, while electrophoretic mobility shift assays were used to assess the binding of the protein to the unmodified and differently modified DNAs.