Kevin O’Malley, Biochemistry and Molecular Biology
“Photochemical Identification of the UK-1 Binding Site on DNA Topoisomerase II”
Faculty Mentor: Dr. Paul J. Smith
Expected Graduation Date: December 2010
The natural product UK-1 is known to catalytically inhibit the enzyme DNA topoisomerase II (topo II) and is also known to kill cancer cells in culture. Our goal is to identify where UK-1 binds to topo II using photoaffinity labeling. We will synthesize a photochemically reactive analog of UK-1 which will covalently attach to the enzyme binding site when irradiated with light. Protein digestion followed by liquid chromatography and mass spectrometry will identify the protein residues attached to UK-1. The results will provide an understanding of the mechanism of inhibition as well as guide the synthesis of better inhibitors related to UK-1 with the long-term goal of identifying clinically useful anti-cancer drugs.
Kevin Machu at Picchu in Peru in 2011.