Scientific article

Optimizing antimicrobial peptide dendrimers in chemical space

Published inAngewandte Chemie: International Edition, vol. 57, no. 28, p. 8483-8487
Publication date2018

We used nearest-neighbor searches in chemical space to improve the activity of the antimicrobial peptide dendrimer (AMPD) G3KL and identified dendrimer T7, which has an expanded activity range against Gram-negative pathogenic bacteria including Klebsiellae pneumoniae, increased serum stability, and promising activity in an in vivo infection model against a multidrug-resistant strain of Acinetobacter baumannii. Imaging, spectroscopic studies, and a structural model from molecular dynamics simulations suggest that T7 acts through membrane disruption. These experiments provide the first example of using virtual screening in the field of dendrimers and show that dendrimer size does not limit the activity of AMPDs.

  • Anti-Bacterial Agents/chemistry/pharmacology
  • Antimicrobial Cationic Peptides/chemistry/pharmacology
  • Dendrimers/chemistry/pharmacology
  • Gram-Negative Bacteria/drug effects
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Dynamics Simulation
Citation (ISO format)
SIRIWARDENA, Thissa N et al. Optimizing antimicrobial peptide dendrimers in chemical space. In: Angewandte Chemie: International Edition, 2018, vol. 57, n° 28, p. 8483–8487. doi: 10.1002/anie.201802837
Main files (1)
Article (Published version)
ISSN of the journal1433-7851

Technical informations

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