Synthesis and binding properties of divalent and trivalent clusters of the Lewis a disaccharide moiety to Pseudomonas aeruginosa lectin PA-IIL.
The synthesis of oligomeric glycocomimetics has been performed for targeting the Pseudomonas aeruginosa PA-IIL lectin, which is of therapeutical interest for anti-adhesive treatment. The disaccharide alpha-L-Fucp-(1-->4)-beta-D-GlcNAc, which is a high-affinity ligand of the lectin, has been coupled to dimeric and trimeric linkers with various lengths and geometries. A series of linear dimers displayed an efficient clustering effect and a very strong affinity, with a lower dissociation constant of 90 nM. The trimeric compound was less efficient in inhibition assays but displayed high affinity in solution. Titration microcalorimetry and molecular modeling allowed in-depth analysis and rationalization of the binding data. These glycoclusters could act by crosslinking the lectins present on the surface of bacteria and therefore interfere with host recognition or biofilm formation.
Marotte
Karine
K
Département de Chimie et Biochimie, Université du Québec à Montréal, Case Postale 8888, Succ. Centre-Ville, Montréal, Québec, Canada.
Préville
Cathy
C
Sabin
Charles
C
Moumé-Pymbock
Myriame
M
Imberty
Anne
A
Roy
René
R
D001665:Binding Sites; D002151:Calorimetry; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
D004187:Disaccharides; D037102:Lectins