NEWS OF THE WEEK
RAIL STRIKE HITS CANADIAN FIRMS TRANSPORTATION: Chemical company executives call on Canadian government to act
A A Canadian National train in brighter times.
STRIKE BY members of the United Transporta tion Union against Canadian National Railway is starting to hurt the bottom line of Canadian chemical producers. Shippers are hoping for a quick end to the strike as the Canadian government gets involved. The strike, over wages and working conditions, be gan on Feb. 10 and has forced the railroad to operate using only management personnel. It is causing con sternation in the Canadian chemical industry and has prompted chemical companies and organizations to call for government action. "Rail service is essential to the Canadian economy, and the strike is beginning to impact our customers and our business," says Chris Pappas, chief operating of ficer of Nova Chemicals. "Since the two parties appear to be at an impasse, we believe it is time for the govern ment to intervene on behalf of Canadian business."
SYNTHETIC ROUTE TO LARGE PROTEINS POLYPEPTIDE SYNTHESIS: H I V
protease analog assembled through kinetic ligation approach
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ITH A PROTEIN SYNTHESIS approach that they first used and reported last year for mak ing a small model protein, researchers now have assembled a much larger protein analog from eas ily modified components. The technique, kinetically controlled ligation (KCL), was developed by chemis try professor Stephen Β. Η. Kent of the University of Chicago and coworkers, who have now extended its applicability to the synthesis of an HIV protease analog (Angew. Chem. Int. Ed. 2007,46,1667). "To the best of our knowledge, the 203-amino-acid
WELL-ASSEMBLED HIV protease analog (ribbon struc ture) synthesized chemically by Kent and Torbeev is shown complexée! with an inhibitor (ball-and-stick structure).
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To meet customer demand, Nova has implemented contingency plans developed in anticipation of the strike. It has reduced production at some of its Cana dian facilities as a precaution. Nova says the financial impact could be significant if the strike is protracted and the company is required to substantially reduce production. In a similar vein, Jeff Johnston, president of Dow Canada, says, "This strike is already having a severe im pact on our ability to ship products, which is affecting our customers." In a letter to Canadian Minister of Labor Jean-Pierre Blackburn, Richard Paton, who is CEO of the Canadian Chemical Producers Association, notes that even the threat of a strike causes disruption as buyers move to suppliers that will not be affected by the work stop page. "Because almost two-thirds of our production is exported," he writes, "our global competitors in other jurisdictions are keenly aware of transportation issues and are prepared to take full advantage in supplying our customers from more dependable sources." In response to the strike, the government has ap pointed a mediator, who has been meeting with union and company representatives. And Blackburn has said he will introduce legislation to end the work stoppage. The union says it will go back to work if the legislation is passed.—WILLIAM STORCK
HIV protease covalent dimer is the protein with the largest linear polypeptide chain ever prepared by total chemical synthesis," Kent says. The technique could make it easier to create protein analogs modified virtually at will for studies of protein function and mechanism and as drug candidates. Kent believes the largest protein made previously by chemical synthesis was a 166-amino-acid erythropoiesis protein that his group created in 2003. That protein was made sequentially—working linearly from one end to the other—using an earlier technique, native chemical ligation (NCL). KCL makes it possible to synthesize proteins convergently—assembling large pieces that are then linked to one another—which is much more efficient and more practical than sequential synthesis. Kent and graduate student Vladimir Torbeev created the 22-kD HIV protease molecule by synthesizing four peptide segments via stepwise solid-phase synthesis, using KCL to combine the segments into two large fragments, and then using NCL to combine the fragments. The product is a single polypeptide chain that folds to form an HIV protease analog with the full enzymatic activity of the native version. The synthesis "illustrates the potential of the convergent synthetic strategy for making larger, more complex protein targets," Kent says. "The work is a tour de force in protein chemical synthesis that showcases the state of the art in peptide ligation technology," comments Tom W. Muir, head of a protein engineering group at Rockefeller University.—STU BORMAN
FEBRUARY 26, 2007
