Publications

We report the design and synthesis of bifunctional phospholipid conjugates, which contain a polymerizable acrylate group and a terminal linker, such as biotin or N-(epsilon-maleimidocaproyl (EMC), to facilitate bioconjugation reactions. The lipid conjugate can be used to generate a multifunctional substrate-supported phospholipid film that is further stabilized via in-situ photocopolymerization.

Phospholipid conjugates of mono- and disaccharides tethered with an n-decanyl spacer were efficiently synthesized via an improved reductive amination of deprotected omega-oxodecanyl beta-glycosides and phosphatidylethanolamines with or without alkenyl groups. The omega-oxodecanyl beta-glycosides were prepared by stereoselective glycosidation of glycosyl halides with 1, 10-decanediol followed by pyridinium dichromate oxidation. The acetyl groups of the omega-oxodecanyl beta-glycosides were removed with sodium methoxide prior to their conjugation with phosphatidylethanolamines.

An efficient synthesis of neoglycophospholipids with variable length alkyl spacer chains is described. Neoglycophospholipids tethered by alkyl chains of 3, 5, 7, 10, and 16 methylene units were synthesized in good overall yields in four steps. The key intermediates, omega-oxoalkyl glycopyranosides, were synthesized in two steps by glycosidation of chloro (or ethylthio) glycosides with a diol followed by oxidation of the remaining hydroxy group to an aldehyde functionality. Conjugation of the omega-glycoalkyl aldehyde with distearoylphosphatidylethanolamine via an improved reductive amination procedure significantly enhanced efficiency and yields with respect to those from traditional procedures. The amphiphilic properties of the neoglycophospholipids were characterized at the air-water interface. While the carbohydrate head group had relatively little effect, the length of the alkyl spacer profoundly influenced surface area-pressure isotherms.