NEWS OF THE WEEK
BRANCHING OUT IN DIFFERENT WAYS CARBOHYDRATE CHEMISTRY:
New synthetic strategy leads to asymmetrically branched N-glycans
the carbohydrate chemist’s toolbox: the ability to easily synthesize libraries of asymmetrically branched N-linked glycans. Without this tool, chemists haven’t been able to use these common molecules—often attached to proteins on cell surfaces—to screen drug candidates and explore ways cells communicate. Now, a strategy developed by Geert-Jan Boons and coworkers at the Complex Carbohydrate Research Center at the University of Georgia changes that. The work could be useful for making carbohydrate arrays for drug discovery and for studying how cell-surface glycans control cell signaling and other biological processes. Unlike nucleic acids and proteins, glycans aren’t made by copying a template but instead are assembled in a customized way by enzymes. And most glycans have highly variable branched structures, which are constructed from sugars. All of that means glycans are hard to synthesize. Chemical synthesis has taken a lot of time, and enzymatic methods have yielded only symmetrically branched glycans. Boons and coworkers’ strategy makes generating diverse glycans easier (Science 2013, DOI: 10.1126/ science.1236231). First, the researchers chemically synthesize a pentasaccharide core structure common to all N-linked glycans. At each of the four sites where branching can occur, they incorporate a different protecting group that can be removed without affecting the others. To make branched glycans, they sequentially remove the protecting groups and add sugar groups to each posi-
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tion. The sugar groups make each branch recognizable by different enzymes, which catalyze the addition of more sugars. The result is a library of asymmetrically branched N-linked glycans. “A similar, although less sophisticated, concept Enzymatic was reported by my group in 2005,” says reactions Yukishige Ito, chief Protecting OR OR scientist in the 1 3 group manipulation Synthetic CelR2O OR4 lular Chemistry Laboratory at RIKEN in Wako, Japan. Protected Asymmetrically pentasaccharide branched Ito’s method core intermediate did produce R = protecting groups asymmetriN-Acetylglucosamine cally branched Mannose glycans, but Galactose Fucose they were limN-Acetylneuraminic acid ited to simpler forms (Angew. Complex N-glycans Chem. Int. Ed. 2005, DOI: 10.1002/anie.200500777). “Boons’s achievement far more convincingly demonFour protecting groups on a strates the strength of the chemoenzymatic strategy in pentasaccharide constructing complex glycan libraries,” Ito says. core can be Boons and coworkers used the new approach to manipulated synthesize about 50 asymmetrically branched glycans. to produce an Working with biologist James C. Paulson of Scripps asymmetrically Research Institute, in La Jolla, Calif., they used some of branched intermediate that the oligosaccharides in microarrays to screen binding is turned into a interactions with proteins such as hemagglutinin from complex mixture different strains of flu virus. of N-linked glycans “The study highlights the advantages of combining via enzymatic insights from chemistry and biology to access comreactions. pounds that would otherwise be difficult to generate,” write Laura L. Kiessling and Matthew B. Kraft of the University of Wisconsin, Madison, in an accompanying Science commentary. “Powerful tools needed to define the functions of specific glycans within the human glycome are now in our purview.”—CELIA ARNAUD
COMMUNITY BUYOUT Sasol makes offer to homeowners near planned chemical project The shale gas revolution is hitting home for a community in Louisiana. In anticipation of building a giant chemical complex at its site in Westlake, La., the South African company Sasol is offering to buy up about 400 properties from residents in a nearby neighborhood long surrounded by chemical plants. Sasol plans to spend up to $21 billion on both a natural-gas-based ethylene cracker and a fuels facility that uses the firm’s gas-to-liquids technology. Together, the company says, the projects represent the single largest manufacturing invest-
ment in the history of Louisiana and one of the largest foreign direct investment manufacturing projects in the U.S. “We recognize that our growth plans will result in the expansion of our facility closer toward our neighbors to the northwest and west of our existing facility,” says Mike Thomas, vice president of Sasol’s U.S. operations. The voluntary buyout program will be run by Community Interaction Consulting, which has administered similar programs around the country. Environmental activists say the chance to move is coming none too soon
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for residents of Mossville, a historic African American community near Sasol and 13 other chemical plants in southwest Louisiana. A local group, Mossville Environmental Action Now, says it has been lobbying for relocation for years because of the effect of industrial pollution on property values and residents’ health. “Environmental justice groups from all over the U.S. and the world are watching what happens in Mossville,” says Michele Roberts of the Environmental Health & Justice Alliance, another activist group.— MICHAEL MCCOY
