title: Coupling of Ligands to the Liposome Surface by Click Chemistry.
abstract: Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Spanedda
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France.
authors.forename: Marcella
authors.initials: M
authors.lastname: De Giorgi
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France.
authors.forename: Fatouma Saïd
authors.initials: FS
authors.lastname: Hassane
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Schuber
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France.
authors.forename: Line
authors.initials: L
authors.lastname: Bourel-Bonnet
authors.affiliation: Laboratoire de Conception et Applications des Molécules Bioactives, Faculté de Pharmacie, UMR 7199 CNRS/Université de Strasbourg, 74 Route du Rhin, 67401, Illkirch, France. frisch@unistra.fr.
authors.forename: Benoît
authors.initials: B
authors.lastname: Frisch
mesh_terms: D057930:Click Chemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry; D008024:Ligands; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*
chemical_list: D008024:Ligands; D008055:Lipids; D008081:Liposomes; D003300:Copper
keywords: Azide-alkyne cycloaddition; Bioconjugation chemistry; Click chemistry; Copper-free click chemistry; Mannose