Optimizing Antimicrobial Peptide Dendrimers in Chemical Space

Angew Chem Int Ed Engl. 2018 Jul 9;57(28):8483-8487. doi: 10.1002/anie.201802837. Epub 2018 Jun 15.


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.

Keywords: antimicrobial agents; chemical space; dendrimers; peptides; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Dendrimers / chemistry*
  • Dendrimers / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Dynamics Simulation


  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Dendrimers