A Fucosylated Lactose-Presenting Tetravalent Glycocluster Acting as a Mutual Ligand of <i>Pseudomonas aeruginosa</i> Lectins A (PA-IL) and B (PA-IIL)—Synthesis and Interaction Studies

A Fucosylated Lactose-Presenting Tetravalent Glycocluster Acting as a Mutual Ligand of <i>Pseudomonas aeruginosa</i> Lectins A (PA-IL) and B (PA-IIL)—Synthesis and Interaction Studies

The Gram-negative bacterium <i>Pseudomonas aeruginosa</i> is an important opportunistic human pathogen associated with cystic fibrosis. <i>P. aeruginosa</i> produces two soluble lectins, the <span style="font-variant: small-caps;">d</span>-galactose-spec...

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Bibliographic Details
Main Authors: Magdolna Csávás, László Kalmár, Petronella Szőke, László Bence Farkas, Bálint Bécsi, Zoltán Kónya, János Kerékgyártó, Anikó Borbás, Ferenc Erdődi, Katalin E. Kövér
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Molecular Sciences
Subjects:
<i>Pseudomonas aeruginosa</i>
lectin
fucosylated lactose
multivalency
saturation transfer difference NMR
Online Access:https://www.mdpi.com/1422-0067/23/24/16194
Description
Summary:The Gram-negative bacterium <i>Pseudomonas aeruginosa</i> is an important opportunistic human pathogen associated with cystic fibrosis. <i>P. aeruginosa</i> produces two soluble lectins, the <span style="font-variant: small-caps;">d</span>-galactose-specific lectin PA-IL (LecA) and the <span style="font-variant: small-caps;">l</span>-fucose-specific lectin PA-IIL (LecB), among other virulence factors. These lectins play an important role in the adhesion to host cells and biofilm formation. Moreover, PA-IL is cytotoxic to respiratory cells in the primary culture. Therefore, these lectins are promising therapeutic targets. Specifically, carbohydrate-based compounds could inhibit their activity. In the present work, a 3-<i>O</i>-fucosyl lactose-containing tetravalent glycocluster was synthesized and utilized as a mutual ligand of galactophilic and fucophilic lectins. Pentaerythritol equipped with azido ethylene glycol-linkers was chosen as a multivalent scaffold and the glycocluster was constructed by coupling the scaffold with propargyl 3-<i>O</i>-fucosyl lactoside using an azide-alkyne 1,3-dipolar cycloaddition reaction. The interactions between the glycocluster and PA-IL or PA-IIL were investigated by isothermal titration microcalorimetry and saturation transfer difference NMR spectroscopy. These results may assist in the development of efficient anti-adhesion therapy for the treatment of a <i>P. aeruginosa</i> infection.
ISSN:1661-6596
1422-0067

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