Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties
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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.
Carroux, C. J., Moeker, J., Motte, J., Lopez, M., Bornaghi, L. F., Katneni, K., ... Poulsen, S-A. (2013). Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties. Bioorganic and Medicinal Chemistry Letters, 23(2), 455 - 459. https://doi.org/10.1016/j.bmcl.2012.11.056