Design, crystal structure and atomic force microscopy study of thioether ligated<scp>d</scp>,<scp>l</scp>-cyclic antimicrobial peptides against multidrug resistant Pseudomonas aeruginosa

He, Runze; Bonaventura, Ivan Di; Visini, Ricardo; Gan, Bee‐Ha; Fu, Yongchun; Probst, Daniel; Lüscher, Alexandre; Köhler, Thilo; Delden, Christian van; Stocker, Achim; Hong, Wenjing; Darbre, Tamis; Reymond, Jean‐Louis

doi:10.1039/c7sc01599b

Cited by 27 publications

(18 citation statements)

References 72 publications

(71 reference statements)

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“…This report builds on our previous examples of using LecB complexes to access structural data for molecules otherwise difficult to crystallize such as oligonucleotides, (32) glycopeptide dendrimer biofilm inhibitors, (33)(34)(35)(36)(37)(38)(39) cyclic and bicyclic AMPs. (40,41) The fucosylated peptides reported here act similarly to SB1 by folding into amphiphilic and membrane disruptive helices. The crystal structures of their LecB complexes show that they mostly form α-helices assembled via hydrophobic contacts into two-helix or four-helix bundles, although two sequences present an unfolded extended structure in their LecB complexes.…”

Section: Introductionmentioning

confidence: 90%

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

et al. 2019

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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 twenty-four 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 αhelices 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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Section: Introductionmentioning

confidence: 90%

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

et al. 2019

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“…Dihedral angles within the thioether linkage vary significantly, even between peptides with the same type of linkage (eg, formed between N‐terminal chloroacetic acid and cysteine). In fact, a peptide with two terminal cysteines that is cyclized using ortho ‐α,α′‐dibromoxylene shows multiple conformations in a single crystal structure with lectin B (PDB 5NF0) …”

Section: Non‐regular Peptidesmentioning

confidence: 99%

Bent into shape: Folded peptides to mimic protein structure and modulate protein function

2020

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“…An important group comprises the primate theta-defensins (e.g., retrocyclins), not found in humans due to a premature stop codon [ 33 , 34 ]. In general, cyclic AMPs are significant for their enhanced stability compared to non-cyclic peptides, which partly explains a considerable interest in their clinical development [ 35 , 36 , 37 , 38 ]. Helical structures can be represented by magainins, cecropins, cathelicidins, and others [ 9 , 10 , 39 , 40 , 41 ].…”

Section: Properties and Limitations Of Natural Cationic Antimicrobmentioning

confidence: 99%

Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

et al. 2020

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The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

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Design, crystal structure and atomic force microscopy study of thioether ligatedd,l-cyclic antimicrobial peptides against multidrug resistant Pseudomonas aeruginosa

Abstract: A new family of cyclic antimicrobial peptides is reported targeting multidrug resistant Pseudomonas aeruginosa by membrane disruption.

Cited by 27 publications

References 72 publications

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

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

Bent into shape: Folded peptides to mimic protein structure and modulate protein function

Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

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