NEWS OF THE W EEK
TAU PROTEIN, SYNTHETICALLY A phosphorylated version of tau protein has been constructed from a 389-amino acid recombinant fragment and a 52-amino acid synthetic fragment.
PROTEIN ENGINEERING:
Researchers make, modify key player in Alzheimer’s disease
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ESEARCHERS IN GERMANY have developed a
method for producing a synthetic version of tau protein labeled with phosphate at a specific site. Being able to make a full version of tau—one of the main actors in Alzheimer’s disease—and to chemically modify it at a specific amino acid site should help scientists uncover more about the mechanism by which tau’s malfunction leads to disease. Normally, tau stabilizes microtubules, which act as scaffolding inside cells such as neurons. But in Alzheimer’s, enzymes add an excessive number of phosphate groups to tau, causing it to dissociate from the microtubules and form tangled fibers inside nerve cells. Although researchers have known about the more than 30 sites on tau that become phosphorylated, says Christian
GEORGIA GULF REBUFFS WESTLAKE PLASTICS: Vinyls firm calls takeover offer ‘opportunistic’
G
EORGIA GULF HAS REJECTED an unsolicited
$1 billion buyout offer from polyvinyl chloride rival Westlake Chemical. The $30.00-per-share offer represents a premium of nearly 23% for Georgia Gulf’s shares over their market close on Jan. 12, the day before the offer was pubFAIR OFFER? Georgia Gulf’s shares spiked licly disclosed. Westlake after Westlake revealed its bid on Jan. 13. had been privately courting Georgia Gulf since last September. Both Georgia Gulf and Westlake make chlorine, vinyl chloride, PVC, and PVC derivatives such as pipe, windows, and doors. Westlake earned $221 million on $3.2 billion in sales in 2010, whereas Georgia NOTE: Data shown through Jan. 17. Gulf made $43 million on WWW.CEN-ONLIN E .ORG
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P. R. Hackenberger of the Free University of Berlin, they haven’t been able to investigate them individually or in desired combinations. That’s because conventional techniques for producing the protein and labeling it with phosphate can’t be controlled site-specifically. Hackenberger’s group has now used expressed protein ligation to achieve the first synthesis of tau protein containing a single phosphorylated site on its C-terminus (Chem. Eur. J., DOI: 10.1002/chem.201103032). The researchers first made a 389-amino acid recombinant fragment of tau in Escherichia coli and then generated a 52-amino acid C-terminal segment with solid-phase peptide synthesis. The shorter fragment contained a phosphorylated serine at its C-terminus and a biotin tag for product purification. To put the two pieces together, the team nudged a thioester on one end of the recombinant fragment and a cysteine on one end of the synthetic segment to react and form a native peptide bond. If this approach can be extended to phosphorylate internal sites on tau, rather than just the C-terminus, says Guy Lippens, a structural biologist at France’s National Center for Scientific Research, “it might lead to a final understanding of the relationship between the physiological and pathological aspects of tau.” Hackenberger says it is conceivable that central regions of tau could be specifically phosphorylated with expressed protein ligation but that it is a long-term goal.—LAUREN WOLF
$2.8 billion in sales. Combined, the two firms would be the second-largest U.S. producer of PVC, after Shintech. Recent years have been tumultuous for Georgia Gulf. It paid $1.6 billion for building products maker Royal Group Technologies in 2006, only to be hit soon thereafter by the housing downturn. In February 2009, the New York Stock Exchange warned the firm that it risked being delisted because its market capitalization had dipped below $75 million. Georgia Gulf officials point out that the firm’s stock traded above $40.00 not long ago. “We believe the Westlake proposal is an opportunistic attempt to acquire the company’s uniquely positioned assets as we recover,” says Georgia Gulf CEO Paul D. Carrico. Westlake retorts that its offer means cash to shareholders sooner rather than later. In a letter to Georgia Gulf’s board members, Westlake CEO Albert Chao chides the board for being “unwilling to discuss” a deal despite the possibility of providing “stockholders with immediate liquidity at a sizable premium in an uncertain economic environment.” Since Jan. 13, Georgia Gulf stock has traded at $3.00 to $4.00 above Westlake’s bid, an indication that the company’s shareholders are looking for a better offer. “We would advise [Georgia Gulf ] shareholders to either wait for a higher offer or wait for the shares to attain levels more in line with the company’s earnings potential,” Charles Neivert, a stock analyst with Dahlman Rose & Co., told clients.—ALEX TULLO
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