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nizes," says Kumar. Because the phenyl alanine carboxyl part of the molecule is hydrophilic and the pyrene part is hy drophobic, Py-Phe will lodge only in A small-molecule-based reagent designed those parts of the protein where a hy to recognize and bind to specific sites in drophilic pocket is very close to a hy proteins can cut the protein backbone drophobic pocket, he explains. "There after irradiation with light. Such reagents aren't many such twin binding sites in a could be very useful for sequencing and given protein." precisely manipulating proteins. Laser flash photolysis studies indicate The photoactive compound is ^ p h e that a Py-Phe cation radical initiates pro nylalanine)-^ 1 -pyrene)butyramide (Py- tein cleavage. This species is formed af Phe). It was designed and investigated by ter excitation from the reaction between Challa V. Kumar, an associate professor of singlet excited-state Py-Phe and an elec chemistry at the University of Connecti tron acceptor, cobalt(III) hexammine. cut, Storrs, and graduate student Apinya The researchers suggest that hydrogen Buranaprapuk, and researchers at Glaxo atom abstraction from the protein back Wellcome, Research Triangle Park, N.C., bone and reaction with oxygen yields a and Columbia University [Proc. Natl. hydroperoxyl radical. Subsequent reac tions involving hydrolysis split the pep Acad. Sci, 95, 10361 (1998)]. "It would be great if there were pho- tide bond. The ability to cleave protein backtocleavage probes for proteins just as there have been for DNA," says Jacque line K. Barton, a chemistry professor at California Institute of Technology. "If C0 2 H [Py-Phe] can be a general reagent for cutting proteins—and that's an impor tant thing that needs to be estab lished—it could very useful for looking at protein and peptide structures and the binding of molecules to proteins and peptides." Ν~(Λ -Phenylalanine)Using two test proteins, a lysozyme 4-(1 -pyrene)butyramide and an albumin, the researchers have es tablished that photocleavage by Py-Phe is highly specific. Py-Phe binds to the ly bones with the use of light has many ad sozyme only at one site, and after irradia vantages. "One can imagine trying to do tion at 344 nm, it efficiently splits the things at a single-molecule level," ex protein into only two pieces. With the plains coauthor and Columbia University albumin, Py-Phe binds to two sites, but chemistry professor Nicholas J. Turro. again the protein is split into only two "With a laser, you can focus precisely so pieces. In one of the albumin binding that you can literally be dealing with one sites, says Kumar, the reagent is not well protein molecule at a time and sequenc oriented for the cleavage reaction. ing it and doing things with it. That kind "We designed the molecule to be very of information and the ability to obtain it discriminating about the sites it recog that precisely are impossible with ther mal means." β With light, there's also a CQ timing feature that can be | exploited to extract a host % of information about how | reactions between proteins °- and things that bind to them occur. "You can pulse a laser so itfiresat femtosec ond or picosecond pulse widths," says Turro. "You can have one photon pro duce something and a sec ond photon acting on that product before it disap pears. All kinds of manipula Buranaprapuk (left) and Kumar designed new tions are possible that are protein snipper.
New protein scissors turned on by light
12 SEPTEMBER 7, 1998 C&EN
completely out of the question by conven tional means." Down the road, Kumar sees potential therapeutic applications. "We could de sign small photoactive molecules that recognize specific proteins related to dis eases," he says. "By shining light on the patient, the bad proteins would break and be deactivated." Maureen Rouhi
Amoco sued over brain cancers Seven former Amoco employees and their families are suing the company, charging that their workplace exposure to toxic chemicals led to cancer. Between 1989 and 1997, six of the plaintiffs were diag nosed with intercranial tumors and one with non-Hodgkin's lymphoma; three plaintiffs have since died. All conducted research in one wing of the Amoco Re search Center in Naperville, HI. The plaintiffs seek compensatory dam ages for medical and legal expenses and punitive damages. The lawsuit wasfiledas a class action, allowing any of the nearly 8,000 employees who have worked at the site to participate. The company, which formed a task force to investigate the illnesses soon after the brain cancers were first diagnosed in 1989 (C&EN, April 27, page 12), was sur prised by the legal action, according to Amoco spokesman Scott Dean. "Our primary concern remains the health and well-being of our current and former colleagues," says Dean. "We intend to continue our investigation into this mys tery and openly communicate what we learn." To date, 12 benign and seven ma lignant intercranial tumors have been diag nosed in current and former employees. According to company accounting rec ords, all of the affected employees worked with catalysts and solvents and had in common 34 chemical R&D projects. The lawsuit, filed in Cook County, 111., circuit court on Aug. 25, claims that Amoco was negligent for not testing all of the research materials used in its facil ity and failing to advise its employees about any potential risk. It also charges that Amoco failed to maintain a safe work environment. Several other companies are named as potential defendants, pending discovery efforts by the plaintiffs' lawyers. Three are chemical companies—BASF, SigmaAldrich, and Henkel—that may have sup-
plied chemicals to the Naperville site. The companies that designed and installed the ventilation system for the building where the cancers occurred also are listed as possible defendants. "Everybody was advised that the working conditions were safe and that no one was being exposed to anything under circumstances that put them at any risk," says plaintiffs' attorney Amanda Hawes of the firm Alexander Law, San Jose, Calif. However, she notes, the lack of Occupational Health & Safety Administration standards for most chemicals combined with the fact that most researchers use combinations of chemicals means that little is known about possible health effects. Determining the source of the cancers, if there is a single source, is very difficult, says Avima M. Ruder, chief of epidemiology at the Cincinnati office of the National Institute for Occupational Safety & Health (NIOSH). She has worked on other brain cancer studies at NIOSH and notes that the variety of chemicals used in the laboratory makes it difficult to link exposure to potential illnesses. Amoco has enlisted the help of medical
specialists at several research institutions. Initial studies—by the University of Illinois, Chicago; the Mayo Clinic, Rochester, Minn.; and the Chicago Institute of Neurosurgery & NeuroResearch—did not link the illnesses to the workplace. After a fourth case was diagnosed in 1996, Amoco commissioned additional research at the University of Alabama, Birmingham, and Johns Hopkins University. Preliminary results from the University of Alabama, presented to Amoco employees in April, indicate that an unusual cluster of one type of brain cancer, called glioma, exists among employees at the Naperville site. But the researchers have not confirmed that the illnesses are related to the workplace. Amoco has scheduled another employee meeting for Oct. 22 to discuss the progress of the cancer investigations. The Alabama team expects to present preliminary results of its studies on mortality and cancer rates for all employees at the Naperville facility, based on their medical histories, and more detail on the tumors that have occurred in employees at that site. Paige Morse
Landmark status for synthetic rubber In front of the starkly modern Polymer Science building of the University of Akron, in Ohio, on Aug. 29, the "cando" spirit of World War II-era chemists was recognized as the American Chemical Society presented its 18th National Historic Chemical Landmark in honor of the 1939-45 U.S. Synthetic Rubber Program. With nearly all natural rubber supplies from Southeast Asia cut off at the start of the war, the efforts in Akron and
University of Akron President Marion 4. Ruebel (left) and Walter unveil the landmark plaque affixed to a stone monument in the university's Buchtel Common; BF Goodrich scientists (above) in 1940.
other U.S. locations by researchers and administrators from government, industry, and academe helped secure the Allied victory. The U.S. Synthetic Rubber Program "was an example of extraordinary teamwork that led to a major scientific achievement," said ACS President Paul H. L. Walter at the dedication ceremony. Rep. Thomas C. Sawyer (D-Ohio) noted that the program "put the nation on a footing to fight a war," supplying a synthetic substitute for the massive amounts of rubber needed for vehicles and equipment. President Franklin D. Roosevelt created the Rubber Reserve Co. (1940)—charged with stockpiling and conserving rubber used in tires. Later, the U.S. Rubber Co. (now Uniroyal), along with Firestone Tire & Rubber Co. (now Bridgestone/Firestone Inc.), BF Goodrich Co., Goodyear Tire & Rubber Co., and Standard Oil Co. of New Jersey (now Exxon Chemical Co.), signed patent and information-sharing agreements concerning synthetic rubber. The companies agreed on a "recipe" for an allpurpose substitute for natural rubber based on "Buna S," a term derived from the sodium polymerization of butadiene developed by researchers at German conglomerate I. G. Farben. Standard Oil of New Jersey, which had a working relationship with I. G. Farben, had begun its own R&D program for largescale production of butadiene from petroleum. Each of the big four rubber companies was engaged in R&D efforts to develop an all-purpose substitute for natural rubber. They formulated a synthetic rubber product known as Government Rub· ber-Styrene, or GR-S. Representatives of each company involved in the GR-S research and production effort were on hand at the historic landmark dedication ceremony. And each company was presented with a replica of the memorial plaque at the university. "As I contemplate the past 60 years of developments in synthetic rubber, I am still impressed with the magnitude of the development of GR-S and many other polymers," said James D. D'lanni, a retired vice president of Goodyear and a former ACS president who did research on monomers that could be polymerized with butadiene. "The interest and talent brought together by the government-sponsored program for industry and academe resulted in a vast outpouring of new polymers for many products of the rubber and polymer industry." William Schulz SEPTEMBER 7, 1998 C&EN
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