11月8日 刘润辉:Antimicrobial Nylon-3 Polymers as Synthetic Mimics of Host Defense Peptide


报告题目:Antimicrobial Nylon-3 Polymers as Synthetic Mimics of Host Defense Peptide
报告人:刘润辉,华东理工大学教授,“青年千人计划”获得者
主持人:程义云 教授
报告时间:2017年11月8日 15:00
报告地点:闵行生科院534小会议室
主办单位:生命科学学院,科技处
 
报告人简介: Professor Runhui Liu obtained B.S. in Pharmaceutical Engineering in 2001 and M.S. in Pesticide Science in 2004 respectively at East China University of Science & Technology (ECUST). He obtained Ph.D in carbohydrate synthesis 2009 at Purdue University. Afterward, he joined Prof. Linda Hsieh-Wilson lab at California Institute of Technology as a postdoc researcher. In 2010, he moved to University of Wisconsin-Madison and worked as a postdoc in Prof. Samuel H. Gellman lab. In 2015, he took a professor position in the School of Materials Science and Engineering at ECUST. His current research focuses on polypeptide polymers in biomedical applications.
 
报告摘要:Drug-resistant microbial infection has been a major challenge to human health. Therefore, considerable effort has been devoted to discovery of new types of antimicrobial agents to battel with drug-resistant microbes. Natural Host defense peptides (HDP) display broad-spectrum antimicrobial activity and low possibility for microbes to develop resistance. However, HDP normally only have moderate activity against bacteria, low stability due to hydrolysis by protease, and high price in preparation. We studied nylon-3 polymers (poly-β-peptides) as mimics of HDP to address above limitations of HDP. These nylon-3 random copolymers have a backbone that is similar to that of HDP and also two key characteristics of HDP, net positive charge and amphiphilicity. These nylon-3 polymers display potent activity against multiple drug-resistant bacterial species, including methicillin-resistant S. aurues (MRSA) and vancomycin-resistant E. faecium (VREF). The best antibacterial nylon-3 also displays very low toxicity toward mammalian cells in hemolytic and cytotoxic studies. Both mammals and fungi are eukaryotes and therefore it is extremely difficult to identify antifungal agents with low toxicity toward the host. Surprisingly, we discover nylon-3 polymers with potent and selective activity against C. albicans, the most common pathogenic fungus in humans. A serial of nylon-3 polymers demonstrate very high activity against multiple drug-resistant strains of C. alibicans. In addition to activity against planktonic fungal cells, nylon-3 polymers also inhibit the formation of C. albicans biofilms and are active against mature C. albicans biofilms.
 
References
(1)Liu, R.; Suarez, J. M.; Weisblum, B.; Gellman, S. H.; McBride, S. M. J Am Chem Soc 2014, 136, 14498.
(2)Liu, R.; Chen, X.; Chakraborty, S.; Lemke, J. J.; Hayouka, Z.; Chow, C.; Welch, R. A.; Weisblum, B.; Masters, K. S.; Gellman, S. H. J Am Chem Soc 2014, 136, 4410.
(3)Liu, R. H.; Chen, X. Y.; Hayouka, Z.; Chakraborty, S.; Falk, S. P.; Weisblum, B.; Masters, K. S.; Gellman, S. H. J Am Chem Soc 2013, 135, 5270.
(4)Liu, R.; Chen, X.; Falk, S. P.; Mowery, B. P.; Karlsson, A. J.; Weisblum, B.; Palecek, S. P.; Masters, K. S.; Gellman, S. H. J Am Chem Soc 2014, 136, 4333.
(5)Liu, R.; Chen, X.; Falk, S. P.; Masters, K. S.; Weisblum, B.; Gellman, S. H. J Am Chem Soc 2015, 137, 2183.