title: Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low-Nanomolar Multivalent Ligands.
abstract: Anti-infectious strategies against pathogen infections can be achieved through antiadhesive strategies by using multivalent ligands of bacterial virulence factors. LecA and LecB are lectins of Pseudomonas aeruginosa implicated in biofilm formation. A series of 27 LecA-targeting glycoclusters have been synthesized. Nine aromatic galactose aglycons were investigated with three different linker arms that connect the central mannopyranoside core. A low-nanomolar (Kd =19 nm, microarray) ligand with a tyrosine-based linker arm could be identified in a structure-activity relationship study. Molecular modeling of the glycoclusters bound to the lectin tetramer was also used to rationalize the binding properties observed.
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institut des Nanotechnologies de Lyon (INL) - UMR CNRS 5270, Ecole Centrale de Lyon, Université de Lyon, 36 Avenue Guy de Collongue, 69134, Ecully cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Dupin
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM) - UMR 5247, CNRS - Université Montpellier - ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Noël
authors.affiliation: 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.
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Carroux
authors.affiliation: Institut des Nanotechnologies de Lyon, UMR CNRS 5270, Université Claude Bernard Lyon 1, Université de Lyon, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Renaud
authors.affiliation: Institut des Nanotechnologies de Lyon (INL) - UMR CNRS 5270, Ecole Centrale de Lyon, Université de Lyon, 36 Avenue Guy de Collongue, 69134, Ecully cedex, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Géhin
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM) - UMR 5247, CNRS - Université Montpellier - ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Meyer
authors.affiliation: Institut des Nanotechnologies de Lyon (INL) - UMR CNRS 5270, Ecole Centrale de Lyon, Université de Lyon, 36 Avenue Guy de Collongue, 69134, Ecully cedex, France.
authors.forename: Eliane
authors.initials: E
authors.lastname: Souteyrand
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM) - UMR 5247, CNRS - Université Montpellier - ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Vasseur
authors.affiliation: Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, CNRS - Université de Lille 1, Cité Scientifique, Avenue Mendeleiev, Bat C9, 59655, Villeneuve d'Ascq cedex, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Vergoten
authors.affiliation: Institut des Nanotechnologies de Lyon (INL) - UMR CNRS 5270, Ecole Centrale de Lyon, Université de Lyon, 36 Avenue Guy de Collongue, 69134, Ecully cedex, France. yann.chevolot@ec-lyon.fr.
authors.forename: Yann
authors.initials: Y
authors.lastname: Chevolot
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM) - UMR 5247, CNRS - Université Montpellier - ENSCM, Place Eugène Bataillon, CC1704, 34095, Montpellier cedex 5, France. morvan@univ-montp2.fr.
authors.forename: François
authors.initials: F
authors.lastname: Morvan
authors.affiliation: 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. sebastien.vidal@univ-lyon1.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D005690:Galactose / Q000737:chemistry* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011550:Pseudomonas aeruginosa / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D018829:Adhesins, Bacterial; C102929:LecA protein, bacteria; C534600:LecB protein, Pseudomonas aeruginosa; D037102:Lectins; D008024:Ligands; D005690:Galactose
keywords: Pseudomonas aeruginosa; glycoclusters; microarrays; multivalency; oligonucleotides