Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia

Magdolna Csávás; Lenka Malinovská; Florent Perret; Milán Gyurkó; Zita Tünde Illyés; Michaela Wimmerová; Anikó Borbás

doi:10.1016/j.carres.2016.11.008

Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from Burkholderia cenocepacia

Carbohydr Res. 2017 Jan 2:437:1-8. doi: 10.1016/j.carres.2016.11.008. Epub 2016 Nov 14.

Authors

Magdolna Csávás¹, Lenka Malinovská², Florent Perret³, Milán Gyurkó¹, Zita Tünde Illyés⁴, Michaela Wimmerová⁵, Anikó Borbás⁶

Affiliations

¹ Department of Pharmaceutical Chemistry, University of Debrecen, POB 78, H-4010 Debrecen, Hungary.
² Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czechia.
³ ICBMS-Equipe CSAp, Université Lyon 1, 69622 Villeurbanne, France.
⁴ Department of Organic Chemistry, University of Debrecen, POB 20, H-410 Debrecen, Hungary.
⁵ Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czechia; National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czechia. Electronic address: michaw@chemi.muni.cz.
⁶ Department of Pharmaceutical Chemistry, University of Debrecen, POB 78, H-4010 Debrecen, Hungary. Electronic address: borbas.aniko@pharm.unideb.hu.

PMID: 27871013
DOI: 10.1016/j.carres.2016.11.008

Abstract

The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal infections in cystic fibrosis patients. Multivalent mannoside derivatives were prepared as potential inhibitors of lectin BC2L-A, one of the virulence factors deployed by B. cenocepacia in the infection process. An (α1→2)-thio-linked mannobioside mimic bearing an azide functionalized aglycon was conjugated to different multivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by azide-alkyne 1,3-dipolar cycloaddition. The interaction between the glycoclusters and the mannose binding BC2L-A lectin from B. cenocepacia was examined by isothermal microcalorimetry, surface plasmon resonance, inhibition of yeast agglutination and analytical ultracentrifugation.

Keywords: Anti-adhesion therapy; Burkholderia cenocepacia; Click reaction; Glycoclusters; Mannose-binding lectin.

MeSH terms

Agglutination Tests
Burkholderia cenocepacia / chemistry*
Calorimetry / methods
Chemistry Techniques, Synthetic
Ligands
Mannose-Binding Lectin / chemistry*
Mannose-Binding Lectin / metabolism
Mannose-Binding Lectin / pharmacology
Mannosides / chemical synthesis
Mannosides / chemistry*
Mannosides / metabolism
Surface Plasmon Resonance
Ultracentrifugation / methods
Yeasts / drug effects

Substances

Ligands
Mannose-Binding Lectin
Mannosides