[Chemical remodelling of cell surfaces in living animals -- metabolic oligosaccharide engineering]
>>Nature 430, 873 - 877 (19 August 2004); doi:10.1038/nature02791
Chemical remodelling of cell surfaces in living animals
JENNIFER A. PRESCHER1,*, DANIELLE H. DUBE1,* & CAROLYN R. BERTOZZI1,2
1 Department of Chemistry, University of California, Berkeley, California 94720, USA
2 Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
* These authors contributed equally to this work
Correspondence and requests for materials should be addressed to C.R.B. (crb@berkeley.edu).
Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. The cell-surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering. This technique has been exploited in fundamental studies of glycan-dependent cell–cell and virus–cell interactions and also provides an avenue for the chemical remodelling of living cells. Unique chemical functional groups can be delivered to cell-surface glycans by metabolism of the corresponding unnatural precursor sugars. These functional groups can then undergo covalent reaction with exogenous agents bearing complementary functionality. The exquisite chemical selectivity required of this process is supplied by the Staudinger ligation of azides and phosphines, a reaction that has been performed on cultured cells without detriment to their physiology. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. The ability to tag cell-surface glycans in vivo may enable therapeutic targeting and non-invasive imaging of changes in glycosylation during disease progression.<<
Cheers, Tuck |
