5D21

Multivalency Effects in Glycopeptide Dendrimer Inhibitors of Pseudomonas aeruginosa Biofilms Targeting Lectin LecA

5D21 の概要

• エントリーDOI: 10.2210/pdb5d21/pdb
• 分子名称: LecA, CALCIUM ION, phenyl beta-D-galactopyranoside, ... (4 entities in total)
• 機能のキーワード: lectin, pseudomonas, multivalency, antimicrobial, biofilm, sugar binding protein
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 52265.87

構造登録者

Bergmann, M.,Michaud, G.,Visini, R.,Jin, X.,Stocker, A.,Darbre, T.,Reymond, J.-L. (登録日: 2015-08-05, 公開日: 2015-11-25, 最終更新日: 2024-01-10)

主引用文献

Bergmann, M.,Michaud, G.,Visini, R.,Jin, X.,Gillon, E.,Stocker, A.,Imberty, A.,Darbre, T.,Reymond, J.L.
Multivalency effects on Pseudomonas aeruginosa biofilm inhibition and dispersal by glycopeptide dendrimers targeting lectin LecA.
Org.Biomol.Chem., 14:138-148, 2016

PubMed Abstract: The galactose specific lectin LecA partly mediates the formation of antibiotic resistant biofilms by Pseudomonas aeruginosa, an opportunistic pathogen causing lethal airways infections in immunocompromised and cystic fibrosis patients, suggesting that preventing LecA binding to natural saccharides might provide new opportunities for treatment. Here 8-fold (G3) and 16-fold (G4) galactosylated analogs of GalAG2, a tetravalent G2 glycopeptide dendrimer LecA ligand and P. aeruginosa biofilm inhibitor, were obtained by convergent chloroacetyl thioether (ClAc) ligation between 4-fold or 8-fold chloroacetylated dendrimer cores and digalactosylated dendritic arms. Hemagglutination inhibition, isothermal titration calorimetry and biofilm inhibition assays showed that G3 dendrimers bind LecA slightly better than their parent G2 dendrimers and induce complete biofilm inhibition and dispersal of P. aeruginosa biofilms, while G4 dendrimers show reduced binding and no biofilm inhibition. A binding model accounting for the observed saturation of glycopeptide dendrimer galactosyl groups and LecA binding sites is proposed based on the crystal structure of a G3 dendrimer LecA complex.

PubMed: 26416170
DOI: 10.1039/c5ob01682g

実験手法

X-RAY DIFFRACTION (1.9 Å)