High-Throughput Synthesis of Antimicrobial Copolymers and Rapid Evaluation of Their Bioactivity

The growing trend in antimicrobial resistance is a potential threat to our society. Due to this, the development of new antimicrobial compounds is urgently required. High-throughput compositional analysis, combined with recent advances in polymerization protocols, allows for rapid production of pote...

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Veröffentlicht in:Macromolecules 2019-06, Vol.52 (11), p.3975-3986
Hauptverfasser: Judzewitsch, Peter R, Zhao, Lily, Wong, Edgar H. H, Boyer, Cyrille
Format: Artikel
Sprache:eng
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Zusammenfassung:The growing trend in antimicrobial resistance is a potential threat to our society. Due to this, the development of new antimicrobial compounds is urgently required. High-throughput compositional analysis, combined with recent advances in polymerization protocols, allows for rapid production of potentially antimicrobial compounds with minimal expertise. This can provide the impetus for correlating activity with composition and functionality. In this study, we have used high-throughput photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization to test the combinations of seven different monomers using 120 different formulations against three distinct bacterial species: Gram-negative Pseudomonas aeruginosa, Gram-positive Staphylococcus aureus, and Mycobacterium smegmatis. Through variations in composition, we have demonstrated the potential of high-throughput PET-RAFT for highly reproducible products, as well as simultaneous testing of multiple variables. Results indicate that primary amines work best against Gram-negative P. aeruginosa, while quaternary ammonium provides activity versus M. smegmatis. Copolymers of these provide avenues for further optimization, especially in the case of quaternary ammonium functionalities.
ISSN:0024-9297
1520-5835
DOI:10.1021/acs.macromol.9b00290