Sterling's OTC operations employ about 5,000 workers worldvyide, while SmithKline employs 52,000. SmithKline has not said how many employees would be affected by the acquisition. But as part of the transaction, it announced a $775 million charge "to cover the cost of integrating [Sterling] and of restructuring and rationalizing the combined businesses." George Peaff
Synthetic receptors bind peptides selectively
Enkephalin substrates are derivatized with dyes to enable simple visual identification of the extent of enkephalin binding to peptidosteroid-containing beads. In one-color assay (left), beads containing peptidosteroid variants are equilibrated with red-dyed enkephalin peptide. Darkest beads can then be isolated to identify peptidosteroids that bind enkephalin with highest affinity. In two-color assay (right), bead-based peptidosteroid library is equilibrated simultaneously with a red-dyed enkephalin and a second blue-dyed enkephalin. A bead turns red if its peptidosteroid binds thefirstenkephalin selectively, a blue bead's peptidosteroid binds the second enkephalin selectively, and a purple bead contains a receptor that binds both enkephalins nonselectively.
Researchers at Columbia University have developed a technique to produce synthetic "receptors" that bind biological substrates larger than those previously accessible with conventional molecular recognition techniques. to a rigid steroid ring system, which The work can potentially be applied they linked to a polystyrene bead. to development of new diagnostic reUsing a split-synthesis method, the reagents, catalysts, and drugs. It was car- searchers made 10,000 peptidosteroid ried out by chemistry professor W. variants, each with a different peptide Clark Still, graduate students Rustum sequence. They tagged each polystyrene Boyce and Ge Li, and postdoctoral as- bead, containing one of the 10,000 possisociates H. Peter Nestler and Toshiro bilities, so the structure of its bound pepSuenaga. The research was published tidosteroid could be easily identified by in the Journal of the American Chemicalgas chromatography. And they attached Society [116, 7955 (1994)]. dye molecules of various colors to the Up to now, molecular recognition four enkephalin substrates so the polystudies have generally focused on ra- styrene beads to which they bound tional design of receptors, or host mol- could be easily distinguished visually. ecules, that bind simple organic or bioSeveral unproductive outcomes were logical compounds. Natural receptors possible—that no member of the recepsuch as antibodies can bind complex tor library would bind or that several biological oligomers like peptides, but receptors (or, indeed, the whole library until now it has not been possible to of receptors) would bind any peptide generate synthetic receptors for such unselectively. large substrates by rational design— What occurred, says Still, "was realpartly because of the high conforma- ly the most interesting outcome of all— tional flexibility of such big molecules. that different members of the library Synthetic receptors have several poten- bound different substrates selectively. tial advantages over antibodies, includ- Although the receptor library couldn't ing higher stability, compatibility with distinguish every enkephalin pair we nonaqueous solvents, smaller size, and ran up against it, it certainly could dismore rapid synthesis and isolation. tinguish some of them. Still and his coworkers sought to de"There's nothing special about the termine if they could find receptors for peptidosteroids," he notes. "In fact, we biological oligomers by using combina- chose a structure that was almost the torial chemistry—techniques in which opposite of what you would choose if a diverse "library" of compounds is you were designing a molecule to be a synthesized and screened to select host structure or receptor." those that bind substrates with high afNevertheless, the combinatorial chemfinity and/or high selectivity. istry technique yielded silk-purse recepTheir goal was to identify simple pep- tors from this library of molecular sow's tidosteroid compounds that might serve ears. 'It isremarkable,"write Still and coas receptors for four enkephalin pen- workers, "that our rather small library tapeptides. The peptidosteroids consist contains receptorlike structures which of two variable peptide chains attached bind and distinguish oligopeptides with
selectivities which would be difficult to engineer by traditional deterministic means." The group has since completed a followup study with a much larger peptidosteroidal library, with which they could distinguish all four enkephalins. The technique is potentially applicable to development of diagnostic agents, selective sensing elements, catalysts, and pharmaceuticals. The best approach for developing new molecules with such desirable properties, write Still and coworkers, "would appear to result from combining a good design with efficient methods for diversity generation and screening." Stu Borman
Rules for bioengineered microorganisms issued The Environmental Protection Agency has proposed a long-awaited rule that would, for the first time, define how it will regulate genetically modified organisms under the Toxic Substances Control Act (TSCA). The agency also has issued a final rule governing field testing of microbial pesticides developed by genetic modification. In a rare moment of unanimity, environmental and industry groups applauded both actions. The proposed rule formalizes EPA's current system for screening new microorganisms. It defines as "new chemical substances," subject to TSCA notification requirements, microorganisms formed by combining genetic materials from orSEPTEMBER 5,1994 C&EN 5
NEWS OF THE WEEK ganisms in different genera. The rule re quires persons intending to manufac ture, import, or process intergeneric or ganisms for commercial purposes to file a Microbial Commercial Activity Notice (MCAN) with EPA at least 90 days be fore undertaking such activity. Introduc tion of such organisms into the environ ment for commercial R&D purposes re quires 60 days' advance notification. EPA also proposes to exempt from the MCAN requirement 10 microor ganisms commonly used in contained fermentation systems to make specialty chemicals, particularly enzymes. R&D testing of intergeneric microorganisms would be exempt from EPA oversight when tests are conducted in contained structures, such as greenhouses or labs. The final rule on field testing chang es the current requirement of advance notification to EPA for even small field tests of genetically modified microbial pesticides. The new rule, issued under the Federal Insecticide, Fungicide & Rodenticide Act, exempts from the re quirement small-scale field tests of or ganisms in which the genetically in duced changes are similar to those that occur in nature. "We're delighted that the agency has persevered and gotten these rules out," says an Environmental Defense Fund
spokeswoman. This "is a big step for ward . . . because for the first time EPA will actually have rules covering bio technology products." A spokesman for BIO, the Biotechnol ogy Industry Organization, couldn't comment in depth on the proposed rule because he hadn't seen it, but says, "We're happy to have a proposed rule to study and comment on. If s been quite
U.S. seeks to boost chemical sales to China U.S.-China commercial ties and U.S. exports to China, including chemical exports, have been given a major boost by a just concluded seven-day mission to China and Hong Kong led by Secre tary of Commerce Ronald H. Brown. The Presidential Business Develop ment Mission to China was the first Cab inet-level visit since the Clinton Admin istration renewed "most favored nation" trade status for China in May and de coupled trade relations from China's hu man rights policies (C&EN, May 30, page 7). Brown was accompanied by two dozen chief executive officers from major U.S. corporations, including At lantic Richfield, Chrysler, Eastman Kodak, Fluor Corp., Foster Wheeler, TRW, and Westinghouse.
Sales brisk for ACS Publications on Disc Susan Barclay of ACS Publications Division displays a page with a full-color illustration from the CD-ROM ver sion of Biochemistry, one of two journals in the justreleased ACS Publications on Disc series. A month after the first discs were shipped, sales are brisk for both Biochemistry and the Journal of the American Chemical Soci ety, says Anthony Durniak, head of ACS Special Publica tions. "Judging from initial interest in these two CD-ROM journals, we expect to expand the series to include many of the 24 ACS journals/' he says. Unlike many text-only or bibliographic CD-ROMs, the ACS discs deliver complete journal pages, including typeset text, chemical equations, and all illustrations. Sophisticated graphics allow users to view entire articles on screen or to print them in black and white or color on their printers. Biochemistry is distribut ed on disc every two months, and JACS, every three months. The discs include the complete text and graphics of issues in that period, as well as cumulative indexes and text for that year. One disc user, professor of chemistry David E. Bergbreiter of Texas A&M University, says the "very fast search feature" speeds up literature searches. Readers can search by author or topic, for key words in the title or abstract, or in a combination of categories. The discs give "very high quality prints," he adds, and are "better archival forms than journals, because you can store 10 years' worth of journals in a few inches of shelf space."
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a period of time under development." He points out that EPA has been operat ing under a 1986 policy statement to reg ulate biotechnology products. "Clearly, they can do that," he says. "But there are a lot of nuances as to how they imple ment the policy" that need to be defined by regulation. The rules were published in the Sept. 1 Federal Register. Janice hong
Delegation members met senior Chi nese officials to advance cooperation on bilateral issues, such as protection of in tellectual property and market access. The CEOs also discussed business agree ments with the Chinese and signed con tracts totaling several billion dollars. A central focus was signing of a "his toric framework agreement" by Brown and Wu Yi, China's Minister of Foreign Trade & Economic Cooperation, who cochair the U.S.-China Joint Commission on Commerce & Trade OCCT). Under the agreement, JCCT bilateral working groups will foster cooperation in several sectors, including chemicals, electronics, electric power, telecommunications, avia tion, automotive machinery, and services. Similar cooperation is envisioned in enviρ
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CD-ROM subscriptions, available in Windows or Macin tosh versions, can be ordered alone or with a subscription to the printed journal. Order information may be obtained from Barclay at (202) 872-6219. Madeleine Jacobs
