Work

β‐1,4‐galactosyltransferase 1 inhibitors modulate cellular N‐glycan profiles

Year: 2026

Type: article

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.

Source: Biotechnology Progress

DOI: 10.1002/btpr.88522

Authors: Jaka Kranjc, Stane Pajk, Marko Anderluh, Anja Pišlar, Matjaž Brinc

Institutions: University of Ljubljana, Novartis (Slovenia)

Language: English

Topic: Viral Infectious Diseases and Gene Expression in Insects

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,160