Optimizing Antimicrobial Peptide Dendrimers in Chemical Space

Siriwardena, Thissa N.; Capecchi, Alice; Gan, Bee-Ha; Jin, Xian; He, Runze; Wei, Dengwen; Ma, Lan; Köhler, Thilo; van Delden, Christian; Javor, Sacha; Reymond, Jean-Louis (2018). Optimizing Antimicrobial Peptide Dendrimers in Chemical Space. Angewandte Chemie (International ed.), 57(28), pp. 8483-8487. Wiley-VCH 10.1002/anie.201802837

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Siriwardena, Thissa Appuhamilage; Capecchi, Alice; Gan, Bee Ha; Jin, Xian; Javor, Sacha and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1433-7851

Publisher:

Wiley-VCH

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

19 Dec 2018 11:54

Last Modified:

17 Jan 2019 13:53

Publisher DOI:

10.1002/anie.201802837

BORIS DOI:

10.7892/boris.122699

URI:

https://boris.unibe.ch/id/eprint/122699

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