Development of high-throughput methods to screen antimicrobial peptoids

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 DESCRIPTION (provided by applicant): Bacterial resistance to antibiotics is a growing problem and even newly generated antibiotics are often ineffective against multi-drug resistant (MDR) bacteria. An increasing number of MDR bacterial infections are occurring in clinical settings, creating life threatening infections for patients already dealing with other conditions. This has driven the development of new antibiotics in an "arms race" of sorts between antibiotic development and bacterial resistance evolution, with antibiotic development lagging behind. However, a new class of antibiotics is being developed by mimicking a naturally occurring defense in many organisms known as AMPs. These AMP mimics are termed "antimicrobial peptoids" and work has indicated that they are potent in killing harmful bacteria, capable of disrupting bacterial biofilms, and relatively stable in the body. Although promising, the work in discovery of these antibiotics has been limited and slow, producing relatively few compounds. The overall goal of this project is to develop a screening method capable of rapidly identifying antimicrobial peptoids for nearly any type of bacteria. Specific work will involve the synthesis o libraries of antimicrobial peptoids on beads. These libraries will be screened in a unique method that allows for rapid identification of compounds capable of preventing bacterial growth. The structures of the best compounds from this screening will be determined by mass spectrometry and their antimicrobial properties characterized to determine how effective this method is at identifying potent antimicrobial agents. It is expected that completion of this proposal and the development of methods to screen large numbers of antimicrobial peptoids rapidly against nearly any bacteria will provide the ability to address dangerous MDR bacteria in a timely fashion.