Structure binding relationship of galactosylated Glycoclusters toward Pseudomonas aeruginosa lectin LecA using a DNA-based carbohydrate microarray.
Pseudomonas aeruginosa (PA) is a major public health issue due to its impact on nosocomial infections as well as its impact on cystic fibrosis patient mortality. One of the main concerns is its ability to develop antibiotic resistance. Therefore, inhibition of PA virulence has been proposed as an alternative strategy to tackle PA based infections. LecA (or PA-IL), a galactose binding lectin from PA, is involved in its virulence. Herein, we aimed at designing high affinity synthetic ligands toward LecA for its inhibition and at understanding the key parameters governing the binding of multivalent galactosylated clusters. Twenty-five glycoclusters were synthesized and their bindings were studied on a carbohydrate microarray. Monosaccharide centered clusters and linear comb-like clusters were synthesized with different linkers separating the core and the galactosyl residues. Their length, flexibility, and aromaticity were varied. Our results showed that the binding profile of LecA to galactosylated clusters was dependent on both the core and the linker and also that the optimal linker was different for each core. Nevertheless, an aryl group in the linker structure drastically improved the binding to LecA. Our results also suggest that optimal distances are preferred between the core and the aromatic group and the core and the galactose.
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS - Université Montpellier 1 - Université Montpellier 2 , place Eugène Bataillon, CC1704, 34095 Montpellier cedex 5, France.
Béatrice
B
Gerland
Alice
A
Goudot
Caroline
C
Ligeour
Gwladys
G
Pourceau
Albert
A
Meyer
Sébastien
S
Vidal
Thomas
T
Gehin
Olivier
O
Vidal
Eliane
E
Souteyrand
Jean-Jacques
JJ
Vasseur
Yann
Y
Chevolot
François
F
Morvan
D018829:Adhesins, Bacterial / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
D018829:Adhesins, Bacterial; C102929:LecA protein, bacteria; D004247:DNA; D005690:Galactose