An efficient system for bioconjugation based on a widely applicable engineered O-glycosylation tag <subtitle>Short title: Controlled bioconjugation via O-glycan engineering</subtitle>
Bioconjugates are an important class of therapeutic molecules. To date, O-glycan-based metabolic glycoengineering has had limited use in this field, due to the complexities of the endogenous O-glycosylation pathway and the lack of an O-glycosylation consensus sequence. Here, we describe the developm...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Book |
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Taylor & Francis Group,
2021-01-01T00:00:00Z.
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| 001 | doaj_cf1665fccfe940a89c94acdca72f40c1 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Thomas V. Murray |e author |
| 700 | 1 | 0 | |a Kasia Kozakowska-McDonnell |e author |
| 700 | 1 | 0 | |a Adam Tibbles |e author |
| 700 | 1 | 0 | |a Annabel Taylor |e author |
| 700 | 1 | 0 | |a Daniel Higazi |e author |
| 700 | 1 | 0 | |a Emmanuel Rossy |e author |
| 700 | 1 | 0 | |a Alessandra Rossi |e author |
| 700 | 1 | 0 | |a Sivaneswary Genapathy |e author |
| 700 | 1 | 0 | |a Giulia Tamburrino |e author |
| 700 | 1 | 0 | |a Nicola Rath |e author |
| 700 | 1 | 0 | |a Natalie Tigue |e author |
| 700 | 1 | 0 | |a Vivian Lindo |e author |
| 700 | 1 | 0 | |a Tristan Vaughan |e author |
| 700 | 1 | 0 | |a Monika A. Papworth |e author |
| 245 | 0 | 0 | |a An efficient system for bioconjugation based on a widely applicable engineered O-glycosylation tag <subtitle>Short title: Controlled bioconjugation via O-glycan engineering</subtitle> |
| 260 | |b Taylor & Francis Group, |c 2021-01-01T00:00:00Z. | ||
| 500 | |a 10.1080/19420862.2021.1992068 | ||
| 500 | |a 1942-0870 | ||
| 500 | |a 1942-0862 | ||
| 520 | |a Bioconjugates are an important class of therapeutic molecules. To date, O-glycan-based metabolic glycoengineering has had limited use in this field, due to the complexities of the endogenous O-glycosylation pathway and the lack of an O-glycosylation consensus sequence. Here, we describe the development of a versatile on-demand O-glycosylation system that uses a novel, widely applicable 5 amino acid O-glycosylation tag, and a metabolically engineered UDP-galactose-4-eperimase (GALE) knock-out cell line. Optimization of the primary sequence of the tag enables the production of Fc-based proteins with either single or multiple O-glycans with complexity fully controlled by media supplementation. We demonstrate how the uniformly labeled proteins containing exclusively N-azido-acetylgalactosamine are used for CLICK chemistry-based bioconjugation to generate site-specifically fluorochrome-labeled antibodies, dual-payload molecules, and bioactive Fc-peptides for applications in basic research and drug discovery. To our knowledge, this is the first description of generating a site-specific O-glycosylation system by combining an O-glycosylation tag and a metabolically engineered cell line. | ||
| 546 | |a EN | ||
| 690 | |a O-glycosylation | ||
| 690 | |a metabolic labeling | ||
| 690 | |a CRISPR | ||
| 690 | |a metabolic glycoengineering | ||
| 690 | |a bioconjugation | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 690 | |a Immunologic diseases. Allergy | ||
| 690 | |a RC581-607 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n mAbs, Vol 13, Iss 1 (2021) | |
| 787 | 0 | |n https://www.tandfonline.com/doi/10.1080/19420862.2021.1992068 | |
| 787 | 0 | |n https://doaj.org/toc/1942-0862 | |
| 787 | 0 | |n https://doaj.org/toc/1942-0870 | |
| 856 | 4 | 1 | |u https://doaj.org/article/cf1665fccfe940a89c94acdca72f40c1 |z Connect to this object online. |