Design and Synthesis of Galactosylated Bifurcated Ligands with Nanomolar Affinity for Lectin LecA from Pseudomonas aeruginosa.
Lectin A (LecA) from Pseudomonas aeruginosa is an established virulence factor. Glycoclusters that target LecA and are able to compete with human glycoconjugates present on epithelial cells are promising candidates to treat P. aeruginosa infection. A family of 32 glycodendrimers of generation 0 and 1 based on a bifurcated bis-galactoside motif have been designed to interact with LecA. The influences both of the central multivalent core and of the aglycon of these glycodendrimers on their affinity toward LecA have been evaluated by use of a microarray technique, both qualitatively for rapid screening of the binding properties and also quantitatively (Kd). This has led to high-affinity LecA ligands with Kdvalues in the low nanomolar range (Kd=22 nm for the best one).
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
Anthony
A
Angeli
Université de Lyon, Institut des Nanotechnologies de Lyon, INL), UMR CNRS 5270, Site Ecole Centrale de Lyon, 36 avenue Guy de Collongue, 69134, Ecully cedex, France.
Muchen
M
Li
Université de Lyon, Institut des Nanotechnologies de Lyon, INL), UMR CNRS 5270, Site Ecole Centrale de Lyon, 36 avenue Guy de Collongue, 69134, Ecully cedex, France.
Lucie
L
Dupin
Unité de Glycobiologie Structurelle et Fonctionnelle, UGSF), UMR 8576 CNRS, Université de Lille 1, Cité Scientifique, Avenue Mendeleiev, Bat. C9, 59655, Villeneuve d'Ascq cedex, France.
Gérard
G
Vergoten
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
Mathieu
M
Noël
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
Mimouna
M
Madaoui
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2, Glycochimie UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France.
Shuai
S
Wang
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
Albert
A
Meyer
Université de Lyon, Institut des Nanotechnologies de Lyon, INL), UMR CNRS 5270, Site Ecole Centrale de Lyon, 36 avenue Guy de Collongue, 69134, Ecully cedex, France.
Thomas
T
Géhin
Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2, Glycochimie UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France.
Sébastien
S
Vidal
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
Jean-Jacques
0000-0002-4379-6139
JJ
Vasseur
Université de Lyon, Institut des Nanotechnologies de Lyon, INL), UMR CNRS 5270, Site Ecole Centrale de Lyon, 36 avenue Guy de Collongue, 69134, Ecully cedex, France.
Yann
0000-0003-3479-3371
Y
Chevolot
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
François
0000-0001-5077-0028
F
Morvan
D018829:Adhesins, Bacterial / Q000378:metabolism*; D050091:Dendrimers / Q000378:metabolism; D015195:Drug Design; D004847:Epithelial Cells / Q000737:chemistry; D006001:Glycoconjugates / Q000627:therapeutic use; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000737:chemistry*; D037521:Virulence Factors / Q000378:metabolism
D018829:Adhesins, Bacterial; D050091:Dendrimers; D006001:Glycoconjugates; C102929:LecA protein, bacteria; D037102:Lectins; D008024:Ligands; D037521:Virulence Factors
LecA; Pseudomonas aeruginosa; glycoclusters; microarrays; multivalency; oligonucleotides