title: Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties.
abstract: A series of novel glycopyranosyl azides were synthesised wherein the carbohydrate moiety was peracylated with four acetyl, propionyl, butanoyl, pentanoyl (valeryl) or 3-methylbutanoyl (isovaleryl) ester linked groups. A panel of glycoconjugates was synthesised from these glycopyranosyl azides using copper-catalysed azide-alkyne cycloaddition. The in vitro metabolic stability, plasma stability and plasma protein binding was then measured to establish the impact of the different acyl group when presented on a common scaffold. The acetyl, propionyl and butanoyl esters exhibited metabolism consistent with esterase processing, and various mono-, di- and tri-acylated hydrolysis products as well as the fully hydrolysed compound were detected. In contrast, the pentanoyl and 3-methylbutanoyl esters were stable.
authors.affiliation: Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, Queensland 4111, Australia.
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Carroux
authors.forename: Janina
authors.initials: J
authors.lastname: Moeker
authors.forename: Josephine
authors.initials: J
authors.lastname: Motte
authors.forename: Marie
authors.initials: M
authors.lastname: Lopez
authors.forename: Laurent F
authors.initials: LF
authors.lastname: Bornaghi
authors.forename: Kasiram
authors.initials: K
authors.lastname: Katneni
authors.forename: Eileen
authors.initials: E
authors.lastname: Ryan
authors.forename: Julia
authors.initials: J
authors.lastname: Morizzi
authors.forename: David M
authors.initials: DM
authors.lastname: Shackleford
authors.forename: Susan A
authors.initials: SA
authors.lastname: Charman
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Poulsen
mesh_terms: D000215:Acylation; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D004355:Drug Stability; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D001386:Azides; D006001:Glycoconjugates; D012709:Serum Albumin; D003300:Copper