Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 16 May 1997:
Vol. 276. no. 5315, pp. 1125 - 1128
DOI: 10.1126/science.276.5315.1125
Prev | Table of Contents | Next

Reports

Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis

Lara K. Mahal, Kevin J. Yarema, Carolyn R. Bertozzi

Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetylmannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. The versatility of this technology was demonstrated by an example of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate.

Department of Chemistry, University of California, Berkeley and Center for Advanced Materials, Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Metabolic glycoengineering: Sialic acid and beyond.
J. Du, M A. Meledeo, Z. Wang, H. S Khanna, V. D P Paruchuri, and K. J Yarema (2009)
Glycobiology 19, 1382-1401
   Abstract »    Full Text »    PDF »
Inaugural Article: Imaging the glycome.
S. T. Laughlin and C. R. Bertozzi (2009)
PNAS 106, 12-17
   Abstract »    Full Text »    PDF »
Site-specific Incorporation of Keto Amino Acids into Functional G Protein-coupled Receptors Using Unnatural Amino Acid Mutagenesis.
S. Ye, C. Kohrer, T. Huber, M. Kazmi, P. Sachdev, E. C.Y. Yan, A. Bhagat, U. L. RajBhandary, and T. P. Sakmar (2008)
J. Biol. Chem. 283, 1525-1533
   Abstract »    Full Text »    PDF »
Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells.
T.-L. Hsu, S. R. Hanson, K. Kishikawa, S.-K. Wang, M. Sawa, and C.-H. Wong (2007)
PNAS 104, 2614-2619
   Abstract »    Full Text »    PDF »
Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo.
M. Sawa, T.-L. Hsu, T. Itoh, M. Sugiyama, S. R. Hanson, P. K. Vogt, and C.-H. Wong (2006)
PNAS 103, 12371-12376
   Abstract »    Full Text »    PDF »
Selective identification of newly synthesized proteins in mammalian cells using bioorthogonal noncanonical amino acid tagging (BONCAT).
D. C. Dieterich, A. J. Link, J. Graumann, D. A. Tirrell, and E. M. Schuman (2006)
PNAS 103, 9482-9487
   Abstract »    Full Text »    PDF »
Effects of Natural Human Antibodies against a Nonhuman Sialic Acid That Metabolically Incorporates into Activated and Malignant Immune Cells.
D. H. Nguyen, P. Tangvoranuntakul, and A. Varki (2005)
J. Immunol. 175, 228-236
   Abstract »    Full Text »    PDF »
Oxidation and Transamination of the 3''-Position of UDP-N-Acetylglucosamine by Enzymes from Acidithiobacillus ferrooxidans: ROLE IN THE FORMATION OF LIPID A MOLECULES WITH FOUR AMIDE-LINKED ACYL CHAINS.
C. R. Sweet, A. A. Ribeiro, and C. R. H. Raetz (2004)
J. Biol. Chem. 279, 25400-25410
   Abstract »    Full Text »    PDF »
Characterization of the Metabolic Flux and Apoptotic Effects of O-Hydroxyl- and N-Acyl-modified N-Acetylmannosamine Analogs in Jurkat Cells.
E. J. Kim, S.-G. Sampathkumar, M. B. Jones, J. K. Rhee, G. Baskaran, S. Goon, and K. J. Yarema (2004)
J. Biol. Chem. 279, 18342-18352
   Abstract »    Full Text »    PDF »
Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides.
S. Goon, B. Schilling, M. V. Tullius, B. W. Gibson, and C. R. Bertozzi (2003)
PNAS 100, 3089-3094
   Abstract »    Full Text »    PDF »
GlcNAc 2-Epimerase Can Serve a Catabolic Role in Sialic Acid Metabolism.
S. J. Luchansky, K. J. Yarema, S. Takahashi, and C. R. Bertozzi (2003)
J. Biol. Chem. 278, 8035-8042
   Abstract »    Full Text »    PDF »
Addition of the keto functional group to the genetic code of Escherichiacoli.
L. Wang, Z. Zhang, A. Brock, and P. G. Schultz (2003)
PNAS 100, 56-61
   Abstract »    Full Text »    PDF »
Biochemical Engineering of Cell Surface Sialic Acids Stimulates Axonal Growth.
B. Buttner, C. Kannicht, C. Schmidt, K. Loster, W. Reutter, H.-Y. Lee, S. Nohring, and R. Horstkorte (2002)
J. Neurosci. 22, 8869-8875
   Abstract »    Full Text »    PDF »
Differential Effects of Unnatural Sialic Acids on the Polysialylation of the Neural Cell Adhesion Molecule and Neuronal Behavior.
N. W. Charter, L. K. Mahal, D. E. Koshland Jr., and C. R. Bertozzi (2002)
J. Biol. Chem. 277, 9255-9261
   Abstract »    Full Text »    PDF »
Versatile Biosynthetic Engineering of Sialic Acid in Living Cells Using Synthetic Sialic Acid Analogues.
C. Oetke, R. Brossmer, L. R. Mantey, S. Hinderlich, R. Isecke, W. Reutter, O. T. Keppler, and M. Pawlita (2002)
J. Biol. Chem. 277, 6688-6695
   Abstract »    Full Text »    PDF »
Surface molecular recognition.
N. S. Sampson, M. Mrksich, and C. R. Bertozzi (2001)
PNAS
   Abstract »    Full Text »    PDF »
A Small-Molecule Modulator of Poly-alpha 2,8-Sialic Acid Expression on Cultured Neurons and Tumor Cells.
L. K. Mahal, N. W. Charter, K. Angata, M. Fukuda, D. E. Koshland Jr., and C. R. Bertozzi (2001)
Science 294, 380-381
   Abstract »    Full Text »    PDF »
Chemical Glycobiology.
C. R. Bertozzi and L. L. Kiessling (2001)
Science 291, 2357-2364
   Abstract »    Full Text »
Biochemical engineering of the N-acyl side chain of sialic acid: biological implications.
O. T. Keppler, R. Horstkorte, M. Pawlita, C. Schmidt, and W. Reutter (2001)
Glycobiology 11, 11R-18R
   Abstract »    Full Text »    PDF »
Rapid determination of the binding affinity and specificity of the mushroom Polyporus squamosus lectin using frontal affinity chromatography coupled to electrospray mass spectrometry.
B. Zhang, M. M. Palcic, H. Mo, I. J. Goldstein, and O. Hindsgaul (2001)
Glycobiology 11, 141-147
   Abstract »    Full Text »    PDF »
Biosynthetic incorporation of unnatural sialic acids into polysialic acid on neural cells.
N. W. Charter, L. K. Mahal, D. E. Koshland Jr., and C. R. Bertozzi (2000)
Glycobiology 10, 1049-1056
   Abstract »    Full Text »    PDF »
Cell Surface Engineering by a Modified Staudinger Reaction.
E. Saxon and C. R. Bertozzi (2000)
Science 287, 2007-2010
   Abstract »    Full Text »
Conversion of cellular sialic acid expression from N-acetyl- to N-glycolylneuraminic acid using a synthetic precursor, N-glycolylmannosamine pentaacetate: inhibition of myelin-associated glycoprotein binding to neural cells.
B. E. Collins, T. J. Fralich, S. Itonori, Y. Ichikawa, and R. L. Schnaar (2000)
Glycobiology 10, 11-20
   Abstract »    Full Text »    PDF »
Nonstatistical binding of a protein to clustered carbohydrates.
N. Horan, L. Yan, H. Isobe, G. M. Whitesides, and D. Kahne (1999)
PNAS 96, 11782-11786
   Abstract »    Full Text »    PDF »
Engineering Novel Cell Surface Receptors for Virus-mediated Gene Transfer.
J. H. Lee, T. J. Baker, L. K. Mahal, J. Zabner, C. R. Bertozzi, D. F. Wiemer, and M. J. Welsh (1999)
J. Biol. Chem. 274, 21878-21884
   Abstract »    Full Text »    PDF »
Metabolic Delivery of Ketone Groups to Sialic Acid Residues. APPLICATION TO CELL SURFACE GLYCOFORM ENGINEERING.
K. J. Yarema, L. K. Mahal, R. E. Bruehl, E. C. Rodriguez, and C. R. Bertozzi (1998)
J. Biol. Chem. 273, 31168-31179
   Abstract »    Full Text »    PDF »
Biochemical Engineering of Neural Cell Surfaces by the Synthetic N-Propanoyl-substituted Neuraminic Acid Precursor.
C. Schmidt, P. Stehling, J. Schnitzer, W. Reutter, and R. Horstkorte (1998)
J. Biol. Chem. 273, 19146-19152
   Abstract »    Full Text »    PDF »
Polyvalent binding to carbohydrates immobilized on an insoluble resin.
R. Liang, J. Loebach, N. Horan, M. Ge, C. Thompson, L. Yan, and D. Kahne (1997)
PNAS 94, 10554-10559
   Abstract »    Full Text »    PDF »
Surface molecular recognition.
N. S. Sampson, M. Mrksich, and C. R. Bertozzi (2001)
PNAS 98, 12870-12871
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)