Biochemistry, Biophysics, and Structural Biology Commons^™

A Study Of The Mammalian High Mobility Group Protein At-Hook 2 (Hmga2) And Its Interactions With Dna, Linjia Su

FIU Electronic Theses and Dissertations

The mammalian high-mobility-group protein AT-hook 2 (HMGA2) is a small DNA-binding protein and consists of three positively charged “AT-hooks” and a negatively charged C-terminal motif. It is a multifunctional nuclear protein linked to obesity, human height, stem cell youth, human intelligence, and tumorigenesis. Previous results showed that HMGA2 is a potential therapeutic target of anticancer and anti‐obesity drugs through inhibiting its DNA‐binding activities. Here a miniaturized, automated AlphaScreen ultra‐high‐throughput screening assay is developed to identify inhibitors targeting HMGA2‐DNA interactions. After screening the LOPAC1280 library, several compounds are identified that strongly inhibit HMGA2‐DNA interactions including suramin, a negatively charged antiparasitic drug. …