Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes.
Synthesis of a distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) conjugate, bearing a hydrazide group at the unattached end of the polymer chain, was achieved using a new heterobifunctional polymeric reagent. The heterobifunctional PEG derivative carrying on one end a reactive succinimidyl carbonate (SC) group and at the other terminal a tert-butyloxycarbonyl (Boc) protected hydrazide group was prepared by an efficient four step process from readily available PEG-2000. The SC-end group of the polymer reacted readily with the amino group of DSPE forming a stable urethane attachment between lipid and PEG. Acidolytic removal of the Boc group yielded a hydrazide-PEG-lipid conjugate suitable for preparation of polymer-grafted liposomes. Taking advantage of the well-documented chemical versatility of hydrazide groups, various biologically relevant ligands can be linked to this type of functionalized liposomes.
Zalipsky
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Liposome Technology, Inc., Menlo Park, California 94025.
D002784:Cholesterol / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D005021:Ethylamines / Q000737:chemistry; D007202:Indicators and Reagents; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000138:chemical synthesis*; D008970:Molecular Weight; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*
D003432:Cross-Linking Reagents; D005021:Ethylamines; D007202:Indicators and Reagents; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D002784:Cholesterol; C016162:triethylamine