Synthesis of Complex Organic Compounds as Potential HDAC2 Inhibitors

Mentors: Siva Dandapani & Carol Mulrooney

Katelyn’s project focused on synthesizing chemical compounds that inhibit an enzyme called HDAC2. HDAC2 inhibitors are of interest as potential treatments for diseases including Alzheimer’s and Parkinson’s. Small molecules that inhibit HDACs are thought to work by loosening the packaging of DNA around histone proteins. Katelyn synthesized all of the compounds in her project using the build/couple/pair technique of synthesizing building blocks, combining them to create all possible isomers, and joining functional groups to create an array of ring systems.

Katelyn’s goal was to synthesize analogs of a compound previously found to inhibit HDAC2, in order to optimize the potency of this compound. She synthesized five chiral building blocks that will be used by other chemists at the Broad to create many analogs of this original HDAC2 inhibitor. Katelyn also completed the synthesis of one analog of the original HDAC2 inhibitor, which will now be tested to see if it successfully inhibits the HDAC2 enzyme.

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Katelyn, a senior at Medford High School, synthesized a collection of chemicals to be tested as inhibitors of histone deacetylase enzymes.