Synthesis of a library of fucosylated glycoclusters and determination of their binding toward Pseudomonas aeruginosa lectin B (PA-IIL) using a DNA-based carbohydrate microarray.
Pseudomonas aeruginosa  (PA) is a Gram negative opportunistic pathogen and is the major pathogen encounter in the cystic fibrosis (CF) lung airways. It often leads to chronic respiratory infection despite aggressive antibiotic therapy due to the emergence of resistant strains and to the formation of biofilm. The lectin PA-IIL (LecB) is a fucose-specific lectin from PA suspected to be involved in host recognition/adhesion and in biofilm formation. Thus, it can be foreseen as a potential therapeutic target. Herein, 16 fucosylated glycoclusters with antenna-like, linear, or crown-like spatial arrangements were synthesized using a combination of DNA solid-phase synthesis and alkyne azide 1,3-dipolar cycloaddition (CuAAC). Their binding properties toward PA-IIL were then evaluated based on DNA directed immobilization (DDI) carbohydrate microarray. Our results suggested that the antenna-like scaffold was preferred to linear or crown-like glycoclusters. Among the crown-like carbohydrate centered fucosylated glycoclusters, mannose-based core was better than glucose- and galactose-based ones. The influence of the linker arm was also evaluated, and long linkers between fucoses and the core led to a slight better binding than the short ones.
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
Gwladys
G
Pourceau
Albert
A
Meyer
Vincent
V
Dugas
Samy
S
Cecioni
Sébastien
S
Vidal
Eliane
E
Souteyrand
Jean-Jacques
JJ
Vasseur
Yann
Y
Chevolot
François
F
Morvan
D001426:Bacterial Proteins / Q000378:metabolism*; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry; D061565:Cycloaddition Reaction; D003510:Cyclohexanes / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry*; D005643:Fucose / Q000737:chemistry*; D037102:Lectins / Q000378:metabolism*; D046228:Microarray Analysis; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa
C569686:Alexa Fluor 647; D001426:Bacterial Proteins; D002232:Carbocyanines; D003510:Cyclohexanes; D004277:DNA, Single-Stranded; D037102:Lectins; D009838:Oligodeoxyribonucleotides; D005643:Fucose; C506365:Cyclohexane