Membrane-active, Synthetic Amphiphiles that Exhibit a Range of Biological Properties

Dr. George W. Gokel, Center for Nanoscience, Departments of Chemistry and Biology, University of Missouri in St. Louis
When Sep 25, 2015
from 01:00 PM to 02:15 PM
Where Ernst Hall, Room 310
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Abstract

The genesis of crown ether chemistry lay in the discovery that they could bind and transport alkali metal cations. Thousands of variations on that theme and myriad applications have been reported. Many substituted crown ethers have amphiphilic properties and can function both as ion carriers and, in a more elaborate embodiment called hydraphiles, they function as ion channels. Hydraphiles and the dialkyl crowns called lariat ethers exhibit a surprising range of biological function on their own and in concert with antibiotics. We have recently found that the presence of hydraphile synthetic pore-forming cation transporters enhance the potency of antibiotics against various microbes when the two are co-administered. Both Gram negative Escherichia coli and Gram positive Bacillus subtilis bacteria have been studied along with the yeast Saccharomyces cerevisiae. The membranes of Gram positive and negative bacteria differ substantially from each other and neither is similar to that of the primary eukaryote. The antibiotics that have been most extensively studied thus far are erythromycin, kanamycin, rifampicin, and tetracycline. These four antibiotics all differ in structure and in their mechanisms of action. Notwithstanding, synergy is observed between the ion transporter and the antibiotics, leading to potency enhancements of >20-fold. Recent studies also show that antibiotic resistance can be reversed in some cases by the presence of these ion complexing and transporting agents.

Speaker's Biography

George Gokel received the B.S. in chemistry from Tulane University and the Ph. D. from the University of Southern California. After post-doctoral work with Nobel Laureate Donald Cram at UCLA, he worked briefly at DuPont's Central Research Department and then began an academic career at the Pennsylvania State University. He subsequently held positions in the Chemistry Departments at the University of Maryland and the University of Miami (Florida). He moved in 1993 to the Department of Pharmacology and Molecular Biology at the Washington University School of Medicine in St. Louis. Since 2006, he has been Distinguished Professor of Science at the University of Missouri in St. Louis and Director of the Center for Nanoscience. He is author or coauthor of over 400 articles, 15 issued patents, and 10 books. He is on the editorial boards of numerous journals and has served as an editor of three of them. He is a fellow of the American Association for the Advancement of Science and, has won the American Chemical Society’s St. Louis Award, the ACS Midwest Award, and the St. Louis Academy of Science’s James B. Eads Award. He was recently elected Fellow of the National Academy of Inventors.