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Optimizing antimicrobial peptide dendrimers in chemical space

Siriwardena, Thissa N
Capecchi, Alice
Gan, Bee-Ha
Jin, Xian
He, Runze
Wei, Dengwen
Ma, Lan
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Published in Angewandte Chemie. 2018, vol. 57, no. 28, p. 8483-8487
Abstract 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 Anti-Bacterial Agents/chemistry/pharmacologyAntimicrobial Cationic Peptides/chemistry/pharmacologyDendrimers/chemistry/pharmacologyGram-Negative Bacteria/drug effectsMicrobial Sensitivity TestsMolecular ConformationMolecular Dynamics Simulation
PMID: 29767453
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Research group Quorom-sensing et gènes de virulence (301)
Swiss National Science Foundation: 200020_159941
Swiss National Science Foundation: IZLCZ2_155982
Swiss National Science Foundation: 407240_167048
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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 https://archive-ouverte.unige.ch/unige:144386

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Deposited on : 2020-11-09

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