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Antibodies 2019, 8(1), 9; https://doi.org/10.3390/antib8010009

Impact of Acetylated and Non-Acetylated Fucose Analogues on IgG Glycosylation

1
Merck Life Sciences, Upstream R&D, Frankfurter Strasse 250, 64293 Darmstadt, Germany
2
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Received: 7 December 2018 / Revised: 2 January 2019 / Accepted: 5 January 2019 / Published: 10 January 2019
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Abstract

The biological activity of therapeutic antibodies is highly influenced by their glycosylation profile. A valuable method for increasing the cytotoxic efficacy of antibodies, which are used, for example, in cancer treatment, is the reduction of core fucosylation, as this enhances the elimination of target cells through antibody-dependent cell-mediated cytotoxicity. Development of fucose analogues is currently the most promising strategy to reduce core fucosylation without cell line engineering. Since peracetylated sugars display enhanced cell permeability over the highly polar free hydroxy sugars, this work sought to compare the efficacy of peracetylated sugars to their unprotected forms. Two potent fucose analogues, 2-deoxy-2-fluorofucose and 5-alkynylfucose, and their acetylated forms were compared for their effects on fucosylation. 5-alkynylfucose proved to be more potent than 2-deoxy-2-fluorofucose at reducing core fucosylation but was associated with a significant higher incorporation of the alkynylated fucose analogue. Acetylation of the sugar yielded only slightly lower fucosylation levels suggesting that acetylation has a minor impact on cellular entry. Even though the efficacy of all tested components was confirmed, results presented in this study also show a significant incorporation of unnatural fucose analogues into the glycosylation pattern of the produced IgG, with unknown effect on safety and potency of the monoclonal antibody. View Full-Text
Keywords: acetylation; CHO cell culture; fucose analogues; IgG fucosylation; incorporation acetylation; CHO cell culture; fucose analogues; IgG fucosylation; incorporation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zimmermann, M.; Ehret, J.; Kolmar, H.; Zimmer, A. Impact of Acetylated and Non-Acetylated Fucose Analogues on IgG Glycosylation. Antibodies 2019, 8, 9.

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