TY - JOUR
T1 - Synthesis of acylated glycoconjugates as templates to investigate in vitro biopharmaceutical properties
AU - Carroux, Cindy J
AU - Moeker, Janina
AU - Motte, Josephine
AU - Lopez, Marie
AU - Bornaghi, Laurent F
AU - Katneni, Kasiram
AU - Ryan, Eileen
AU - Morizzi, Julia
AU - Shackleford, David
AU - Charman, Susan Ann
AU - Poulsen, Sally-Ann
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.sciencedirect.com/science/article/pii/S0960894X12015089
U2 - 10.1016/j.bmcl.2012.11.056
DO - 10.1016/j.bmcl.2012.11.056
M3 - Article
VL - 23
SP - 455
EP - 459
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 2
ER -