Molecular Design, Structures, and Activity of Antimicrobial Polymers As Synthetic Mimics of Host-Defense Peptides
Prof. Kenichi Kuroda
University of Michigan
Ann Arbor, Michigan
The emergence of antibiotic resistant bacteria “superbugs” is a significant public health concern. The prevalence of drug resistance rapidly diminishes the available treatment options. Although an urgent need of new antibiotics is well-documented, the number of new antibiotics has fallen steadily in the last few decades. This is because it is a scientific challenge to find molecular mechanisms that can overcome bacterial resistance mechanisms and do not contribute to resistance development.
Our research is focused on a new molecular design of antimicrobial polymers as synthetic mimics of naturally occurring host-defense antimicrobial peptides. These peptides exert their antimicrobial effect by acting on bacterial cell wall or membranes, which contrast to conventional antibiotics. We synthesized methacrylate random copolymers with primary ammonium and alkyl groups to mimic the cationic amphiphilic functionality of these peptides. The copolymers displayed antimicrobial activity against a broad spectrum of bacteria including antibiotic-resistant Staphylococcus aureus. Bacteria cultured with the copolymers did not develop resistance after 21 passages while the inhibitory concentration of conventional antibiotics increased up to 500 times. This polymer design has been extended to include different polymer structures/architectures such as amphiphilic block copolymers and degradable polymers.
Antimicrobial polymers offer a great deal of promise for development of new antimicrobial agents which are not susceptible to the resistance mechanisms in bacteria. Compared to antimicrobial peptides, synthetic polymers can be produced in much greater quantities and provide a flexible framework for chemical modification and adaptation. The chemical and structural diversity of polymers will expand the possibilities for new antimicrobial materials with tailored activity.
Kenichi Kuroda received his B. Eng. in Polymer Chemistry and M. Eng. in Biological Chemistry from Kyoto University, Japan. He joined Prof. Toyoichi Tanaka's group at the Department of Physics in the Massachusetts Institute of Technology and studied the volume phase transition of polymer gels. After Prof. Tanaka passed away in 2000, Prof. Timothy Swager at the MIT chemistry department became his supervisor. He continued his doctoral research on polymer gels as well as semi-conducting polymers for biosensors in Prof. Swager's group and earned his Ph.D. in Physical Chemistry from MIT in 2003. Prior to joining the faculty at the University of Michigan School of Dentistry in 2006, he was a postdoctoral researcher in Prof. William DeGrado's group at University of Pennsylvania School of Medicine and developed antimicrobials based on polymeric materials. His current research interests include the development of biologically active polymers.
Monday, October 14
Michael's Restaurant at Shoreline Park Mountain View, CA 94043
6 PM social hour
7 PM dinner
8 PM lecture
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Breast of Chicken, Portobello