25th Annual Stauffer Lectureship (Day 2 of 2): Professor Jacqueline Barton, Caltech (Hosts: Ed Solomon & Keith Hodgson)
About the Talk
"Targeting DNA Mismatching"
Deficiencies in the repair of DNA mismatches are associated with several different cancers, as well as the resistance of cancers to commonly used chemotherapeutics. Our laboratory has developed bulky rhodium complexes that target DNA mismatches through metalloinsertion. These octahedral complexes include an expansive tetracyclic aromatic ligand that can only be accommodated by DNA at a thermodynamically destabilized mismatch site. The first generation compound, Rh(bpy)2chrysi3+ (chrysi = 5,6-chrysenequinone diimine), binds 80% of all possible DNA mismatches and with remarkable specificity for the mismatched site. High resolution crystal structures of metal complexes bound to single base mismatches within a DNA oligonucleotide duplex reveal the distinctive binding mode of metalloinsertion at the mismatched site, where the mismatched bases are ejected, replaced by the metallonsertor. The family of metalloinsertors shows selective cytotoxicity to cells deficient in mismatch repair. Targeting of genomic DNA mismatches provides a unique cell-selective strategy in the design of novel chemotherapeutics.
About the Speaker
Dr. Jacqueline K. Barton is the John G. Kirkwood and Arthur A. Noyes Professor of Chemistry at the California Institute of Technology. Barton was awarded the A.B. at Barnard College and a Ph.D. in Inorganic Chemistry at Columbia University. After a postdoctoral fellowship at Bell Laboratories and Yale University, she became an assistant professor at Hunter College, City University of New York. Soon after, she returned to Columbia University, becoming a professor of chemistry after three years (1986). In the fall of 1989, she joined the faculty at Caltech and served as the Norman Davidson Leadership Chair of the Division of Chemistry and Chemical Engineering from 2009 to 2019.
Professor Barton has pioneered the application of transition metal complexes to probe recognition and reactions of double helical DNA. In particular, she has carried out studies to elucidate electron transfer chemistry mediated by the DNA double helix, a basis for understanding DNA damage, repair, and replication. Through this research, Barton has trained more than 100 graduate students and postdoctoral students. Barton has also served the chemistry community through her service on government and industrial boards.
Barton has received many awards. These include the NSF Alan T. Waterman Award, the American Chemical Society (ACS) Award in Pure Chemistry, a MacArthur Foundation Fellowship, and most recently the National Academy of Sciences’ Award in the Chemical Sciences. She has been elected to the American Academy of Arts and Sciences, the American Philosophical Society, the National Academy of Sciences, the National Academy of Medicine, along with an honorary fellowship in the Royal Society of Chemistry. In 2011, Dr. Barton received the 2010 National Medal of Science from President Obama, and in 2015, she received the ACS Priestley Medal, the highest award of the ACS.