Synthesis of Designer Lipids Using "Click" Chemistries

            Liposomes have great potential in the fields of drug delivery, imaging and in simplified cell membrane studies.  However, to achieve their full potential in these applications, it frequently becomes necessary to incorporate synthetic constructs and new functionalities into the membrane architecture.  We have created a simplified method for incorporation of functional groups of interest into the phospholipid structure through the covalent attachment of a second aliphatic tail onto a lysolipid backbone.  This addition is now possible through the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC), thiol-acrylate and/or thiol-Michael reactions using lysolipids functionalized with an alkyne, thiol, or acrylate group, respectively.  This wide range of chemistries enables more simplified synthesis of lipids containing variable chemical moieties and enables the covalent attachment of these functionalized tails using a range of catalysts.  In the end, this approach will ease the testing of liposome systems containing new behaviors and characteristics.