title: Synthesis of dodecavalent fullerene-based glycoclusters and evaluation of their binding properties towards a bacterial lectin.
abstract: Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12,000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie, Organique 2-Glycochimie, UMR 5246, Université Claude Bernard Lyon 1 and CNRS, 43 Boulevard du 11 Novembre 1918, 69622, Villeurbanne, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Cecioni
authors.forename: Vincent
authors.initials: V
authors.lastname: Oerthel
authors.forename: Julien
authors.initials: J
authors.lastname: Iehl
authors.forename: Michel
authors.initials: M
authors.lastname: Holler
authors.forename: David
authors.initials: D
authors.lastname: Goyard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Praly
authors.forename: Anne
authors.initials: A
authors.lastname: Imberty
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nierengarten
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D057930:Click Chemistry; D057075:Enzyme Assays; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism*; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D006386:Hemagglutination Tests; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D000480:Alkynes; D001386:Azides; D001426:Bacterial Proteins; D037741:Fullerenes; D006001:Glycoconjugates; D037102:Lectins