Bioconjugation for potent antimicrobial peptides development
报告时间：2022年10月12日 9:00
报告地点：腾讯会议ID：400 322 578，密码：7573
报告人：Wenyi Li
主办单位：球友会
报告题目：Bioconjugation for potent antimicrobial peptides development
报告人简介：
Dr Wenyi Li received his doctoral degree from School of Chemistry at the University of Melbourne under the supervision of Prof John D Wade and Prof Frances Separovic. His doctoral thesis of antimicrobial peptides development has been awarded the Graham Johnston Best Thesis Award from Royal Australian Chemical Institute and Monica Reum Memorial Prize from the University of Melbourne. After two years of postdoctoral experience with Prof Christian Hackenberger supported by Leibniz-DAAD fellowship in Germany, in December 2018, he has moved back to the University of Melbourne as a research fellow to work on the development of antimicrobial agents with Prof Neil O’Brien-Simpson and Prof Greg Qiao. He and his collaborators focus on the development of antimicrobial agents, including antimicrobial peptide and peptide-based polymers.
报告简介：
Since the discovery of penicillin and subsequent antibiotics, the increasing global consumption and inappropriate use of these ‘wonder’ drugs has played a critical role in driving antimicrobial resistance (AMR) in the last two decades at an alarming rate as assessed by World Health Organization (WHO)1. Antimicrobial peptides (AMPs), known as host defense peptides, are potentially potent alternatives to conventional antibiotics given their broad-spectrum of activity2-4. Proline-rich AMPs (PrAMPs) show broad-spectrum activity against Gram-negative bacteria via both a multimodal mechanism of action and immunostimulatory activity.
Our earlier studies showed that the de novo designed PrAMPs, Chex1-Arg20, undergoes a change of mechanism of interaction with Gram-negative membranes upon multimerization from its linear monomeric form containing a C-terminal hydrazide to either a discontinuous dimer or tetramer5. Our current studies have explored the effect of dimerization of this peptide via C-terminal Cys thiol addition to a series of bifunctional linkers to determine the effect of orientation of the peptides and the length between them on antimicrobial activity6. In vitro assays confirmed that dimerization per se significantly enhanced Chex1-Arg20 action and that dimer-peptides exhibited particularly strong action against multi-drug resistant bacteria as well as preformed biofilms. The immunomodulatory activity of the lead candidates were also found to neutralise inflammation by reducing nitroxide releasing Studies investigating the mode of action indicated these dimer PrAMPs can interact with both outer and cytoplasmic membranes to affect membrane potential and stress responses in the bacteria.
Our findings highlight the advantages of modern chemical biology methods to develop novel C-terminal-modified multimerized PrAMPs having both more potent and broad spectrum antibacterial activity.