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Updated: May 17, 2026

FtsZ Polymerization Assays: Simple Protocols and Considerations
Published on: November 16, 2013
A bactericidal guanidinomethyl biaryl that alters the dynamics of bacterial FtsZ polymerization
Malvika Kaul1, Ajit K Parhi, Yongzheng Zhang
1Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School , Piscataway, New Jersey 08854-5635, USA.
Abstract:
The prevalence of multidrug resistance among clinically significant bacterial pathogens underscores a critical need for the development of new classes of antibiotics with novel mechanisms of action. Here we describe the synthesis and evaluation of a guanidinomethyl biaryl compound {1-((4'-(tert-butyl)-[1,1'-biphenyl]-3-yl)methyl)guanidine} that targets the bacterial cell division protein FtsZ. In vitro studies with various bacterial FtsZ proteins reveal that the compound alters the dynamics of FtsZ self-polymerization via a stimulatory mechanism, while minimally impacting the polymerization of tubulin, the closest mammalian homologue of FtsZ. The FtsZ binding site of the compound is identified through a combination of computational and mutational approaches. The compound exhibits a broad spectrum of bactericidal activity, including activity against the multidrug-resistant pathogens methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), while also exhibiting a minimal potential to induce resistance. Taken together, our results highlight the compound as a promising new FtsZ-targeting bactericidal agent.
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