Structural Biology/Biochemistry Seminar
11:15 am – 12:30 pm | 112 KLB
Tuesday October 28, 2014
“Phosphomimetic peptide inhibitors of DNA repair: development, structure, and function”
Dr. Matthew Hartman
Virginia Commonwealth University
Host: Dr. Lei Zhu
We are pursuing several different areas of cancer chemical biology research.
Protein-protein interaction inhibitors
Traditional small molecule drug discovery for protein-protein interaction inhibitors has routinely disappointed. The Hartman Lab has developed a powerful process for the development of inhibitors of protein-protein interactions that involves a technique known as mRNA display. The power of this approach is that we can effectively search for inhibitors from cyclic peptide libraries containing over 1013 unique variants, dramatically enhancing our chances of finding a viable inhibitor. We can make these peptides more stable to degradation through the incorporation of modified, “unnatural” amino acids. We are focusing our efforts on development of inhibitors of DNA repair protein complexes that can be used to sensitize cancer cells towards chemotherapy and radiation.
Drug delivery with light
New methods for selective delivery of drugs to the sites of tumors promise to reduce the awful side effects of cancer chemotherapy. We have developed a new strategy to deliver therapeutic agents into cancer cells with light. To achieve this we attach a cancer chemotherapy drug to a cell impermeable small molecule via a light cleavable linker. The resulting conjugates are completely inactive in the dark, but upon illumination become active and cytotoxic to cancer cells.
New means for detection of small quantities of important biological analytes with fluorescence promise to make diagnosis of diseases simple. Using an azido pyrene derivative, we have achieved selective fluorogenic detection of hydrogen sulfide, a gaseous signaling compound. Relative to other sensors, our molecule is highly water soluble, making it ideal for detection of hydrogen sulfide in biological fluids.