nium nitrate plant was totally destroyed. Several of the warehouses were totally destroyed." Complete site assessment is expected to take up to a month. Joyce says the company's insurance will cover workers' compensation, property replacement costs, third-party liability, and lost profits from business interruption. "We are expecting [to put aside] reserves against this that could be $5 million" to pay insurance deductibles and items not covered by insurance, he notes. The Port Neal plant, built in 1967, ac-
But Klug and coworkers point out counted for 15% of the company's nitrogen fertilizer production (including ca- that zinc-finger proteins can also enpacity from the Oct. 20 acquisition of hance gene expression by binding to Agricultural Minerals & Chemicals). The gene-activation domains—a role that oliplant contributed $11 million, about gonucleotide agents cannot play. Indeed, 25% of Terra's operating income for the in their Nature paper, they report anothfirst nine months of 1994. It had capac- er experiment in which the oncogene ity of 350,000 tons per year for anhy- DNA sequence is used as a promoter for drous ammonia. Of that, 85% was up- expression of another gene. They show graded into other products, including that the designed protein, linked to a do500,000 tons of nitrogen solutions for fer- main that activates transcription, suctilizer, 100,000 tons of urea, and about cessfully switches on the gene. 60,000 tons of ammonium nitrate. According to Klug, "The experiments Elisabeth Kirschnerso far prove the principle that one can design a novel protein for recognizing a given sequence of DNA, in this case an oncogene. However, we still need to refine and develop methods of getting tic leukemia. The protein binds specifi- proteins into cells. Ultimately, we may be cally to the sequence and inhibits ex- able to insert a gene into cells to enable them to manufacture their own blocking pression of the oncogene. The protein was created by combina- proteins, and this is one of the areas we'll torial and rational design techniques. be looking into now/' Stu Bortnan Klug and coworkers identified an initial set of zinc fingers that bound the oncogene sequence by isolating them from phage-display libraries of randomized zinc fingers. They then refined the structures by rational design, based on known recognition rules for Tenneco plans to sell its U.K.-based zinc-finger binding. Use of a DNA-binding protein with chemical subsidiary, Albright & Wilzinc fingers to target gene sequences is son, through a public offering. The sale similar conceptually to antisense and tri- will leave Tenneco with no chemical ple-helix-binding strategies, in which operations. The Houston-based firm expects to RNA- and DNA-binding oligonucleotides sell 100% of A&W during the first quarare used to inhibit gene expression. ter of 1995, with the shares offered only in the U.K. and listed on the London Stock Exchange. The total number of Zinc finger is stabilized shares to be offered and tentative offerby zinc coordination ing price per share have yet to be set. The move continues Tenneco's shed(xXx) (srix) ding of units to focus on its core businesses of packaging, automotive parts, (N) (T) and natural gas pipelines. "A&W's con® ® version to a separate publicly traded (M) (X) company will substantially increase the resources andflexibilitywe are generating to grow our core businesses/' notes Dana G. Mead, chairman and chief executive officer of Tenneco and chairman of N terminus ^^K)... A&W. Tenneco already has sold the C terminus public 55% of its Case Corp. farm & conConsensus sequence for three struction equipment subsidiary. zinc finger domains in protein As an autonomous company, A&W designed by Klug and coworkers likely will rank as the fourth largest inC = cysteine, E = glutamic acid, F = phenylalanine, G = glycine, H = histidine, dependent chemical maker in the U.K. I = isoleucine, K = lysine, L = leucine, in terms of sales, says Jeremy Chantry, M = methionine, N = asparagine, Q = glutamine, R = arginine, U.K. chemicals analyst at BQeinwort BenR/K = arginine or lysine, S = serine, T = threonine, X = variable residue son in London. He notes that Tenneco tried, and failed, to sell A&W previous-
Designed protein represses leukemia gene A designed protein containing "zinc fingers" that bind specific DNA sequences in a leukemia gene has been found to stop uncontrolled cell growth in mouse cells. This is the first time a DNA-binding protein has been engineered de novo to inhibit gene expression, suggesting the potential for development of a new class of therapeutic medicines. The work was carried out by Yen Choo, Isidro Sanchez-Garcia, and Aaron Klug of the Medical Research Council Laboratory of Molecular Biology, Cambridge, England. It is described in last week's Nature [372,642 (1994)]. James A. Wells of Genentech, whose research interests include zinc-finger proteins, says Klug and coworkers have shown that "a designed repressor can actually regulate a gene of interest. That's an important next step to take in demonstrating that designed zinc fingers could be useful in gene therapy." A zinc finger is a DNA-binding domain in a protein. The domain's folded structure is stabilized by a zinc ion coordinated to four amino acid residues. Klug first proposed the zinc-finger concept in 1985. Since then, researchers have shown that many eukaryotic DNA-binding proteins contain zincfinger structures. Earlier this year, Klug and coworkers showed that zinc fingers can discriminate between closely related DNA triplets (three-nucleotide sequences). They also proposed that zinc fingers could be linked together to form structures that could recognize longer DNA sequences. Now, they have created a protein with three zinc-finger domains—each designed to bind to one DNA triplet in a nine-nucleotide sequence in the oncogene responsible for acute lymphoblas-
Tenneco plans to sell Albright & Wilson unit
DECEMBER 19,1994 C&EN
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