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 α-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.
Key wordsLiposome Azide-alkyne cycloaddition Bioconjugation chemistry Click chemistry Mannose
- 5.Schuber F (1995) Chemistry of ligand-coupling to liposomes. In: Philippot JR, Schuber F (eds) Liposomes as tools in basic research and industry. CRC Press, Boca Raton, pp 21–39Google Scholar
- 8.Schuber F, Said Hassane F, Frisch B (2007) Coupling of peptides to the surface of liposomes – Application to liposome-based synthetic vaccines. In: Gregoriadis G (ed) Liposome technology, 3rd edn. Informa Healthcare, New York, USA, pp 111–130Google Scholar
- 18.Hein CD, Liu XM, Wang D (2008) Click chemistry, a powerful tool for pharmaceutical sciences. Pharm ResGoogle Scholar
- 21.Cavalli S, Tipton AR, Overhand M, Kros A (2006) The chemical modification of liposome surfaces via a copper-mediated [3 + 2] azide-alkyne cycloaddition monitored by a colorimetric assay. Chem Commun (Camb):3193–3195Google Scholar