news of the week M AY 5, 20 0 8 E D I T E D BY W I L L I A M G. SC H U L Z & K I M B E R LY R . T WA M B LY
CARBOHYDRATES: Technique
is ‘global positioning system’ for tracking glycans in organisms
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COU RT ESY O F CA RO LY N B E RTOZ Z I A N D COWO R K E RS
Cell-surface glycans shine in this microscopy image of the head of a three-day-old zebrafish embryo treated with the new technique.
rinated cyclooctyne (DIFO) reagents (Proc. Natl. Acad. Sci. USA 2007, 104, 16793; C&EN, Oct. 22, 2007, page 15). This ligation reaction is faster than the Staudinger ligation and is nontoxic, unlike the copper-catalyzed click chemistry reactions on which it’s based. In the new study the researchers introduce azide-derivatized N-acetylgalactosamine (GalNAc) metabolically into developing zebrafish embryos and treat the embryos with DIFO reagent to fluorescently label GalNAc-containing glycans. They then use microscopy to image the labeled glycans in the developing animals (Science 2008, 320, 664). The technique makes it possible for Bertozzi and coworkers to detect increases in glycan biosynthesis in specific locations during zebrafish development and to visualize patterns of glycan expression that previously
HE FIRST TECHNIQUE for imaging carbohydrates as they are produced on cell surfaces of live animals has been developed by glycobiology specialist Carolyn R. Bertozzi and coworkers at the University of California, Berkeley. Specific glycan (oligosaccharide) structures in cells are important SHINY REACTION Glycans in live zebrafish embryos markers and mediators light up when the embryos are fed azide-derivatized of many physiological Probe N-acetylgalactosamine (GalNAc) and then treated with processes, but up to now difluorinated cyclooctyne (DIFO) reagents to attach fluorescent NH changes in these glycans probes to GalNAc-containing glycans. couldn’t be visualized in Probe O living organisms. F AcO OAc O NH The new technique, F O based on cell-friendly OAc O AcO F N fluorescent-labeling O HN N F 3 chemistry devised by the N N N3 O same group, will help scientists more closely Azide-derivatized GalNAc DIFO probe the functional roles of carbohydrates during Ac = acetyl development and in both health and disease. would have been undetectable. The researchers believe Chemistry professor M. G. Finn of Scripps Research Institute says the Bertozzi group’s technique “provides the technique can be extended to other sugars, such as a ‘global positioning system’ for tracking carbohydrates sialic acid. The new study represents “a significant advance in through organisms. This is chemical biology at its finvisualizing the distribution of sugars on cell surfaces, est: refined and reliable chemical tools illuminating— where they are believed to mediate cell adhesion, militerally—molecular interactions in gration, and recognition processes,” says glycan-imagliving biological systems.” ing specialist Mary L. Kraft of the University of Illinois, In recent years, Bertozzi and coworkUrbana-Champaign. “Changes in cell-surface glycans ers have developed techniques for imagalso occur during embryo development and are charing glycans in live cells. First, they feed acteristic of several diseases, such as cancer. However, azide-derivatized sugars to live organhow they mediate these processes is largely unknown” isms, which incorporate the modified because no methods have existed to visualize them in sugars into their glycans. After cells are live animals. The ability of the new approach “to deterremoved from the organisms, the lamine how glycans are distributed spatially within a tisbeled glycans can be imaged by using the sue and in time can shed light on their functional roles Staudinger ligation, a reaction developed and help identify cell-surface markers indicative of the by Bertozzi’s group in 2000, to mark the physiological status of cells.” glycans with fluorescent probes. But that Chemistry Nobel Prize winner K. Barry Sharpless of reaction and similar ones are too slow or Scripps, who helped develop the concept of click chemtoo toxic for use in live animals. istry, comments that Bertozzi’s “in vivo light-up of the Last year, Bertozzi’s group developed zebrafish is a stunning first.”—STU BORMAN copper-free click chemistry with difluoW W W.C E N - O N L I N E .O RG
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M AY 5, 20 0 8
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SUGARS IMAGED IN LIVE ANIMALS
