5NES

Discovery, crystal structures and atomic force microscopy study of thioether ligated D,L-cyclic antimicrobial peptides against multidrug resistant Pseudomonas aeruginosa

Summary for 5NES

• Entry DOI: 10.2210/pdb5nes/pdb
• Descriptor: Fucose-binding lectin II (PA-IIL), CYD-TRP-TRD-LYS-LYD-LYS-LYD-LYS-TRD-TRP-CYD, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: cyclic peptides, antimicrobials, pseudomonas aeruginosa, sugar binding protein
• Biological source: Pseudomonas aeruginosa; More
• Total number of polymer chains: 5
• Total formula weight: 49803.41

Authors

Reymond, J.-L.,Darbre, T.,Stocker, A.,Hong, W.,van Delden, C.,Koehler, T.,Luscher, A.,Visini, R.,Fu, Y.,Di Bonaventura, I.,He, R. (deposition date: 2017-03-11, release date: 2017-09-13, Last modification date: 2024-01-17)

Primary citation

He, R.,Di Bonaventura, I.,Visini, R.,Gan, B.H.,Fu, Y.,Probst, D.,Luscher, A.,Kohler, T.,van Delden, C.,Stocker, A.,Hong, W.,Darbre, T.,Reymond, J.L.
Design, crystal structure and atomic force microscopy study of thioether ligated d,l-cyclic antimicrobial peptides against multidrug resistant Pseudomonas aeruginosa.
Chem Sci, 8:7464-7475, 2017

PubMed Abstract: Here we report a new family of cyclic antimicrobial peptides (CAMPs) targeting MDR strains of . These CAMPs are cyclized a xylene double thioether bridge connecting two cysteines placed at the ends of a linear amphiphilic alternating d,l-sequence composed of lysines and tryptophans. Investigations by transmission electron microscopy (TEM), dynamic light scattering and atomic force microscopy (AFM) suggest that these peptide macrocycles interact with the membrane to form lipid-peptide aggregates. Amphiphilic conformations compatible with membrane disruption are observed in high resolution X-ray crystal structures of fucosylated derivatives in complex with lectin LecB. The potential for optimization is highlighted by -methylation of backbone amides leading to derivatives with similar antimicrobial activity but lower hemolysis.

PubMed: 29163899
DOI: 10.1039/c7sc01599b

Experimental method

X-RAY DIFFRACTION (1.606 Å)