Conjugation of ligands to the surface of preformed liposomes by click chemistry.
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 alpha-1-thiomannosyl ligands, functionalized with an azide group to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields were obtained in the presence of bathophenanthrolinedisulphonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage was triggered by this conjugation reaction and the coupled mannose ligands were 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. Efficient copper-free azide-alkyne click reactions are, however, being developed, which should alleviate this constraint in the future.
Frisch
Benoît
B
Départment de Chimie Bioorganique, Faculté de Pharmacie, Institut Gilbert Lautriat, UMR 7175-LC1 CNRS-Université Louis Pasteur, Strasbourg-Illkirch, France.
Hassane
Fatouma Saïd
FS
Schuber
Francis
F
D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry*; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D003500:Cyclization; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D008358:Mannose / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties
D000480:Alkynes; D001386:Azides; D008024:Ligands; D008081:Liposomes; D003300:Copper; D008358:Mannose