Synthesis of high-mannose type neoglycolipids: active targeting of liposomes to macrophages in gene therapy.
The concise synthesis of five biantennary oligomannose neoglycolipids is presented. Employing a strategy based on the principles of reactivity tuning and orthogonal activation, the oligomannose moieties, isolated from the glycoprotein 63 of the parasite Leishmania mexicana amazonensis, were rapidly assembled taking advantage of common structural motifs found in these N-glycans. Deprotection of all structures was achieved in high yield by hydrogenolysis. The deprotected glycoconjugates were subsequently coupled to a cholesteroldiamine derivative using diethylsquarate as a linker. The resulting neoglycolipids will be used as additives to cationic liposome formulations in the active targeting of liposomes to macrophages.
Düffels
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Department of Chemistry, University of Cambridge, UK.
Green
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LG
Ley
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SV
Miller
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AD
D002240:Carbohydrate Sequence; D004337:Drug Carriers; D015316:Genetic Therapy; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000032:analysis*; D008969:Molecular Sequence Data; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004337:Drug Carriers; D006017:Glycolipids; D008081:Liposomes; D008358:Mannose