title: Chemoenzymatic synthesis of oligohyaluronan-lipid conjugates.
abstract: Herein, we describe an efficient and high-yielding method to synthesize hyaluronan oligosaccharide-lipid conjugates. This strategy is based on first covalently attaching diphytanoyl glycerophosphatidylethanolamine (DiPhPE) to commercially available high molecular weight hyaluronic acid (HA), via the carboxylate group of the glucuronic acid using carbodiimide chemistry. The HA-lipid conjugate mixture is then digested with bovine testicular hyaluronidase to yield HA-DiPhPE conjugates that have a narrow distribution of moderately sized HA oligosaccharides. These HA-lipid conjugates can be incorporated into liposomes or micelles to selectively target CD44 that is overexpressed on many cancer or cancer initiating cells.
authors.affiliation: Departments of Bioengineering, Therapeutic Sciences, and Pharmaceutical Chemistry, University of California San Francisco , 513 Parnassus Avenue, San Francisco, California 94143-0912, United States.
authors.forename: Dipali
authors.initials: D
authors.lastname: Ruhela
authors.forename: Saul
authors.initials: S
authors.lastname: Kivimäe
authors.forename: Francis C
authors.initials: FC
authors.lastname: Szoka
mesh_terms: D000818:Animals; D019556:COS Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis* / Q000737:chemistry*; D008297:Male; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry*; D013737:Testis / Q000201:enzymology
chemical_list: D008055:Lipids; D009844:Oligosaccharides; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase