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Updated: May 22, 2026

Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
β-1,4-galactosyltransferase 1 inhibitors modulate cellular N-glycan profiles
Jaka Kranjc1, Stane Pajk2, Marko Anderluh2
1Institute for Pharmacy, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Abstract:
N-glycosylation is a key post-translational modification of proteins influencing their physicochemical properties as well as biological activity. This study investigates the in vivo activity of four β-1,4-galactosyltransferase 1 inhibitors in cell cultures producing recombinant IgG antibodies. Inhibitors, previously identified as potent inhibitors in on-target assay, were evaluated in fed-batch bioprocesses. Dose-dependent effects on cell culture performance were assessed following compound addition. N-glycan profiles were analyzed using InstantPC labeling and UHPLC-FLD, while intracellular compound concentrations were quantified via LC-MS/MS following time-resolved sampling of treated cell lysates. Bioprocess parameters, including cell growth, viability, and productivity, were monitored throughout cultivation. The study revealed divergent behaviors between on-target potency and in vivo activity, underscoring the importance of cellular permeability, metabolic stability, and off-target effects of potential inhibitors used in cell culture. These findings provide new insights into the challenges of glycosylation pathway modulation and inform strategies for future glycoengineering tool development.
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