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X-ray Crystal Structures of Short Antimicrobial Peptides as Pseudomonas aeruginosa Lectin B Complexes

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Baeriswyl Stéphane, Gan Bee-Ha, Siriwardena Thissa N., Visini Ricardo, Robadey Maurane, Javor Sacha, Stocker Achim, Darbre Tamis, Reymond Jean-Louis,
Project Chemical Space Design of Small Molecules and Peptides
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Original article (peer-reviewed)

Journal ACS Chemical Biology
Volume (Issue) 14(4)
Page(s) 758 - 766
Title of proceedings ACS Chemical Biology
DOI 10.1021/acschembio.9b00047

Abstract

Herein, we report X-ray crystal structures of 11–13 residue antimicrobial peptides (AMPs) active against Pseudomonas aeruginosa as complexes of fucosylated d-enantiomeric sequences with the P. aeruginosa lectin LecB. These represent the first crystal structures of short AMPs. In 24 individual structures of eight different peptides, we found mostly α-helices assembled as two-helix or four-helix bundles with a hydrophobic core and cationic residues pointing outside. Two of the analogs formed an extended structure engaging in multiple contacts with the lectin. Molecular dynamics (MD) simulations showed that α-helices are stabilized by bundle formation and suggested that the N-terminal acyl group present in the linker to the fucosyl group can extend the helix by one additional H-bond and increase α-helix amphiphilicity. Investigating N-terminal acylation led to AMPs with equivalent and partly stronger antibacterial effects compared to the free peptide.
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