Skip Navigation


Glycobiology Advance Access originally published online on May 22, 2006
Glycobiology 2006 16(9):833-843; doi:10.1093/glycob/cwl004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
16/9/833    most recent
cwl004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (14)
Right arrow Disclaimer
Google Scholar
Right arrow Articles by DeFrees, S.
Right arrow Articles by Clausen, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DeFrees, S.
Right arrow Articles by Clausen, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli

Shawn DeFrees3, Zhi-Guang Wang3, Ruye Xing3, Arthur E. Scott3, Jin Wang3, David Zopf1,3, Dominique L. Gouty4, Eric R. Sjoberg4, Krishnasamy Panneerselvam4, Els C. M. Brinkman-Van der Linden2,4, Robert J. Bayer4, Mads A. Tarp5 and Henrik Clausen5

3 Neose Technologies, Inc., 102 Witmer Road Drive, Horsham, PA 19044; 4 Neose Technologies, Inc., 6330 Nancy Ridge Road, Suites 102–103, San Diego, CA 92121; and 5 Department of Medical Biochemistry and Genetics, Glycobiology, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark

1 To whom correspondence should be addressed; e-mail: dzopf{at}neose.com

2 Present address: Noordwijkerhout 2211 AR, Schaepmanlaan 19, The Netherlands

Received on February 8, 2006; revised on May 11, 2006; accepted on May 13, 2006

Covalent attachment of polyethylene glycol, PEGylation, has been shown to prolong the half-life and enhance the pharmacodynamics of therapeutic proteins. Current methods for PEGylation, which rely on chemical conjugation through reactive groups on amino acids, often generate isoforms in which PEG is attached at sites that interfere with bioactivity. Here, we present a novel strategy for site-directed PEGylation using glycosyltransferases to attach PEG to O-glycans. The process involves enzymatic GalNAc glycosylation at specific serine and threonine residues in proteins expressed without glycosylation in Escherichia coli, followed by enzymatic transfer of sialic acid conjugated with PEG to the introduced GalNAc residues. The strategy was applied to three therapeutic polypeptides, granulocyte colony stimulating factor (G-CSF), interferon-alpha2b (IFN-{alpha}2b), and granulocyte/macrophage colony stimulating factor (GM-CSF), which are currently in clinical use.

Key words: G-CSF / glycosylation / GM-CSF / IFN-{alpha}2b / PEGylation


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 GlycobiologyHome page
L. M Willis, M. Gilbert, M.-F. Karwaski, M.-C. Blanchard, and W. W Wakarchuk
Characterization of the {alpha}-2,8-polysialyltransferase from Neisseria meningitidis with synthetic acceptors, and the development of a self-priming polysialyltransferase fusion enzyme
Glycobiology, February 1, 2008; 18(2): 177 - 186.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
S. Bernatchez, M. Gilbert, M.-C. Blanchard, M.-F. Karwaski, J. Li, S. DeFrees, and W. W Wakarchuk
Variants of the {beta}1,3-Galactosyltransferase CgtB from the Bacterium Campylobacter Jejuni have Distinct Acceptor Specificities
Glycobiology, December 1, 2007; 17(12): 1333 - 1343.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
P. Norberg, S. Olofsson, M. A. Tarp, H. Clausen, T. Bergstrom, and J. A. Liljeqvist
Glycoprotein I of herpes simplex virus type 1 contains a unique polymorphic tandem-repeated mucin region
J. Gen. Virol., June 1, 2007; 88(6): 1683 - 1688.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
M. A. Tarp, A. L. Sorensen, U. Mandel, H. Paulsen, J. Burchell, J. Taylor-Papadimitriou, and H. Clausen
Identification of a novel cancer-specific immunodominant glycopeptide epitope in the MUC1 tandem repeat
Glycobiology, February 1, 2007; 17(2): 197 - 209.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.