Under primordial conditions, amino acids can form peptides via two routes R
R Ο I II H2NCHCOH
Unknown intermediate
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R I C H - C - N - •CH H I HNVN COH CH
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COS R Ο I II H2NCHCOH
Dipeptide
R
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but in this system the rate of peptide bond formation is faster than the rate of hydrol ysis, so a steady-state yield of dipeptides is produced." Wàchtershàuser, who holds a doctorate in organic chemistry, works as a patent attorney in Munich. His work is funded by Germany's main research grant agency, Deutsche Forschungsgemeinschaft (DFG), an unusual situation for someone who has no laboratory of his own. Huber—"she
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R 0 1 II H 2 NCHCOH
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H N
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does all the work," Wàchtershàuser tells C&EN—carries out their research in borrowed lab space at the Technical University of Munich. "We do not assume there was a prebiotic broth" of small organic molecules that served as the building blocks for life, Wàchtershàuser says. "Everything happened where volcanoes belched very hot gases out of early Earth." Pamela Zurer
. ·. and RNA needs no help from proteins to make peptides
P
roteins dominate the chemistry of living systems today. But they may not have always done so. Before proteins, many evolutionary chemists argue, there was RNA, and as molecular systems in the prebiotic world evolved, it may have been RNA that catalyzed most of their chemistry. One of the most compelling pieces of evidence that a world dominated by RNA catalysis may have preceded contemporary biochemistry is the complex cellular structure called the ribosome that orchestrates modern-day protein synthesis. Ribosomes contain both RNA and proteins; for example, three RNAs and about 55 proteins in the bacterium Escherichia coli. Evidence has been mounting for at least 15 years that the critical function of the ribosome—that
of linking the proper amino acids together to form peptide bonds—is performed by one of the RNA segments, called 23S in E. coli. Now Kimitsuna Watanabe and his colleagues in the department of chemistry and biotechnology at the University of Tokyo have shown that 23S RNA alone can catalyze the peptide-bond-forming step of protein synthesis. Furthermore, the researchers have divided this piece of RNA into six segments or domains, synthesized each of these separately, and shown that the peptide-forming activity is localized to one specific domain of the molecule [Science, 281,666(1998)]. Watanabe's experiments are "one of the strongest pieces of evidence that RNA alone can catalyze peptide bond formation," says Paul R. Schimmel, professor of
molecular biology and chemistry at Scripps Research Institute, La Jolla, Calif. "It's a very important result," says Rachel Green, assistant professor of molecular biology and genetics at Johns Hopkins University medical school, Baltimore. "It's the first direct evidence for what has been an exciting hypothesis for a long, long time: that RNA is the active center of these ancient molecules." The finding is being greeted with caution by many researchers. "It's such a big result that one should be very careful in its interpretation," Green says. One cause of concern is that the Watanabe experiments show only a relatively modestfivefoldincrease in activity over a fairly high background level. "In my heart of hearts, I think their result is right, fundamentally," Green says. "But it has to be very carefully established that their increase in activity is really significant and repeatable." The Japanese researchers made each domain of 23S RNA synthetically from its gene to ensure that it would not contain any traces of ribosomal proteins. They then tested each domain separately and in various combinations for ability to catalyze peptide bond formation. Only systems containing domain V showed this ability. That domain was active alone, but it had enhanced activity when mixed with certain other domains, suggesting that the fragments of the molecule associate into a functional whole, the researchers propose. "The one piece of the RNA that had the activity was exactly the piece that all the genetic and chemical work over the past 20 years had led people to predict was where the catalytic center had to be," Schimmel notes. "That's pretty convincing." Rebecca Rawls
Hercules gets into water treatment Hercules hasfinallymade the big deal it has been seeking for so long. Late last week, it reached a definitive agreement to acquire Trevose, Pa.-based water treatment company BetzDearborn for $2.4 billion in cash and the assumption of $700 million in debt. In one fell swoop, Hercules will boost annual sales to $3.2 billion by adding BetzDearborn's $1.3 billion in 1997 sales to its own $1.9 billion. When the deal closes in the fourth quarter—subject to government and BetzDearborn shareholder approvals—Hercules will have boosted itself from 37th to 24th among AUGUST 3, 1998 C&EN 7
n e w s of t h e w e e k C&EN's Top 100 U.S. chemical producers (C&EN, May 4, page 22). The new Hercules will have a combined workforce of 13,400 employees, 80 manufacturing plants, and seven major research centers. And although the two companies say their combination "is driven more by growth opportunities than cost savings, both companies agree they can capture a minimiim of $100 million in synergies." Says Hercules Chairman and Chief Executive Officer R. Keith Elliott, "This transaction is a superb combination of two complementary businesses that will create the world's premiere paper chemical business and also give us a new franchise in chemical treatment of water and industrial process systems." It is an especially sweet deal for Elliott, who tried to arrange the purchase of National Starch from its Anglo Dutch parent, Unilever, in 1997, but lost it to London-based ICI. Just six months ago, his hostile tender offer for Britain's Allied Colloids failed in the face of a stronger bid from Switzerland-based Ciba Specialty Chemicals. Elliott and William R. Cook, BetzDearborn chairman, president, and CEO, will become coCEOs of Hercules. Elliott will retain the chairman's title, and Cook will become vice chairman. Cook and three other BetzDearborn directors will join Hercules' board, increasing it from 10 to 14 members. Marc Reiscb
Rohm and Haas picks two for top posts Succession should be smooth at Rohm and Haas, which has named two long-time executives to take over the company's top posts this year and next. Rajiv L. Gupta, currently vice president
Gupta (left) and Fitzpatrick don't anticipate major changes.
8 AUGUST 3, 1998 C&EN
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for electronic materials and Asia-Pacific, will succeed J. Lawrence Wilson, chairman and chief executive officer since 1988, when Wilson retires by the end of 1999. Gupta, 52, who started his career with Rohm and Haas in 1971 as a financial analyst, will be named vice chairman, effective January 1999. J. Michael Fitzpatrick, currently vice president and chief technology officer, will succeed John P. Mulroney, president and chief operating officer since 1986, at the end of this year. Fitzpatrick, 51, joined the company in 1975 after completing a research fellowship at Harvard University and a Ph.D. in chemistry at Rice University. Not surprisingly for homegrown executives, the two don't anticipate making major changes at the company. Fitzpatrick notes that he and Gupta have been on the chairman's committee for the past three years and helped formulate strategy during that time. In fact, although the new jobs don't formally start until January, Gupta says Rohm and Haas expects to complete all necessary internal reorganization by the end of September, so that a new executive team can enter 1999 at full speed. Gupta says he will continue to position Rohm and Haas as "a growth-oriented spe-
cialty chemicals company." However, growth through acquisition has been lacking in recent years given high prices and the firm's strict financial criteria. Rohm and Haas's most recent deals have been sales— early this year it left joint ventures with France's Elf Atochem and Germany's Rohm. Fitzpatrick acknowledges that the obvious acquisition candidates are often out of Rohm and Haas's price range, particularly in electronic materials, a segment targeted to double to 20% of company sales by 2001. "The trick is to find the not-so-obvious ones," he says, citing as a good example last year's purchase of an interest in Rodel, a supplier of chemical mechanical polishing slurries to semiconductor makers. Gupta adds that both the electronics and chemical industries are going through downturns that could lower asset prices. "Maybe patience will pay off," he says. In the meantime, Rohm and Haas is rewarding shareholders with a 3-for-l stock split and an $800 million stock buyback that Gupta says will increase earnings per share and return on equity. The company says it will still have the capacity to make more than $1 billion in debt-financed acquisitions after the buyback. Michael McCoy
Human tests of pesticides raise ethical concerns
nonprofit group, has called on EPA to impose a moratorium on human testing and to establish strict guidelines for such testing. Strict federal guidelines do exist for medical research involving humans, but no oversight system is in place to ensure that humans involved in pesticide experiments are protected, says EWG. The group's president, Ken Cook, claims, "Human tests enable chemical companies to eliminate safety factors that have long been applied when nonhuman animals are used for testing." EPA says it is "deeply concerned that some pesticide manufacturers seem to be engaging in health effects studies on human subjects as a way to avoid more protective results from animal tests under the new Food Quality Protection Act (FQPA)." The act requires EPA to add up therisksof pesticides with common modes of action and regulate them as one. EPA has not banned human tests, and it has used results from such tests in initial risk calculations, says Dave L. Cohen, a spokesman for the EPA administrator's office. He says the agency will be asking the Science Advisory Board, an outside panel of scientists, to make sure the federal guidelines on the ethics of tests involving
Since 1992, four trials in which human volunteers were paid to ingest pesticides have been conducted in U.K. labs and, according to U.S. Environmental Protection Agency officials, more human tests are probably under way. Last year, Amvac Chemical Corp., City of Commerce, Calif., commissioned an English lab to conduct three feeding trials of dichlorvos, an ingredient in pet flea and tick collars, on paid volunteers. In 1992, Rhône-Poulenc Agro, Lyons, France, paid a lab in Scotland to test aldicarb, an extremely toxic insecticide, on humans. In all the studies, levels of cholinesterase—an enzyme that affects brain and nerve cells— fell in subjects eating insecticide but returned to normal after the trial ended. Human studies are generally done to avoid application of a 10-fold safety factor to permissible residue levels when extrapolating healthrisksfrom animal data to humans. But the Environmental Working Group (EWG), a Washington, D.C.-based
