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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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"Biomimetic Drugs: In Vitro, In Vivo & Mechanistic Studies of 5-12mer Antibacterial Peptoids to Treat Respiratory Infections"
Annelise E. Barron, Ph.D.
Associate Professor of Bioengineering
Stanford School of Medicine & School of Engineering
Growing bacterial resistance to conventional antibiotics has spurred the exploration of bioengineered antimicrobial peptides (AMPs) and mimetics as novel anti-infective agents. However, since peptide bioavailability is limited by proteolysis, non-natural AMP mimics are interesting as more robust and biostable analogues of AMP and seem to offer distinct advantages as potential clinical therapeutics. We report here on our experimental exploration of the development of poly-N-substituted glycines (peptoids) as a new class of biomimetic antimicrobial drugs, via multiple approaches including several different in vitro assays and in vivo mouse studies. After studying more than 120 peptoid sequence variants, we identified a number of unique peptoids that exhibit potent, broad-spectrum antibacterial in vitro activity, and which have a unique, biomimetic mechanism of action: bacterial rigidification. In our recent in vivo testing, mice were infected intratracheally with bioluminescent Pseudomonas aeruginosa, then treated by our TM5 peptoid, providing a significant reduction in bacterial loads compared to untreated animals. TM5 peptoid was also well tolerated in the lung by mice. In addition, new super-resolution fluorescence videomicroscopy studies confirm that these peptoids rapidly “rigidify” bacterial cytoplasm, just like natural cathelicidin AMPs. Taken together, these results show the highly promising potential clinical applicability of these 5-12mer peptoids.
