would be no way to determine whether or how to attempt to clean up the mate rial, Smith adds. John McCarthy, vice president of global scientific and regulatory affairs at the American Crop Protection Asso ciation (ACPA), agrees: "Those con cerned with an emergency should have a way to deal with it." U.S. firms can legally manufacture and export banned pesticides and pes ticides that were never tested or regis tered in the U.S. However, notes Mc Carthy, ACPA member companies do not export banned or severely restrict ed pesticides. And he objects to calling most unregistered pesticides hazard ous. Many are registered in another country, he says. Companies voluntarily send notices to the Environmental Protection Agency when they are exporting banned, severe ly restricted, and unregistered pesticides, and EPA—under the prior-informed consent law—informs the importing country of the pesticide's status. But be cause most shipping records lack the pesticide's name, and many lack the producer's name, EPA has no way to monitor compliance. FASE is concerned about health ef fects resulting from banned, restricted, and highly toxic pesticides, especially on farm workers in developing nations who usually lack U.S.-required protec tive clothing and respirators. To remedy some of these problems, FASE urges that export of banned and never-registered pesticides be out lawed and that EPA be required to keep accurate, publicly available records of pesticide production and ex port. McCarthy agrees that changes in the regulations are needed so EPA can monitor compliance with the priorinformed-consent law. Bette Hileman
Polyvalent inhibitors may lead tofludrugs Selectively unfastening a polymer from enzyme sites on the surface of the in fluenza virus enhances the polymer's ability to prevent the virus from adher ing to red blood cells, chemists at Har vard University have shown. The researchers are studying binding of the flu virus to red blood cells with the ultimate goal of designing effective
sides' group at Harvard, binds to both neuraminidase and Two ligands act together to hemagglutinin and inhibits the boost inhibition of flu virus flu virus's ability to adhere to red blood cells. The polyacryl Polyacrylamide amide is derivatized with backbone multiple side chains carrying sialic acid groups linked to the chains via the sugars' α-car bons. The researchers chose to use an α-carbon linkage so neuraminidase—which normal ly attacks an α-hydroxy link age—couldn't clip sialic acid • = Sialic acid Y = Hemagglutinin from the polymer and thereby Y = Neuraminidase = Neuraminidase inhibitor escape its clasp. The researchers believe the polymer works in HO H OH two ways to keep the virus from attaching to red blood cells: It binds extremely tightly to the Sialic acid surface of the virus, and it helps (N-acetylneuraminic acid) keep the virus and cells apart through steric stabilization—a phenomenon in which hydroNeuraminidase inhibitor philic polymers prevent particles H NH^^COOH in colloidal solutions from clumping together. In the absence of a neuraminidase inhibi Now, Whitesides, Seok-Ki tor, polyacrylamides with dangling sialic Choi, and Mathai Mammen acid tails bind to glycoproteins hemagglu have added a neuraminidase tinin and neuraminidase on the surface of inhibitor—a sialic acid analog— the flu virus, blocking the virus from bind along with the derivatized ing to red blood cells. Adding a neuramin polymer to the virus-red blood idase inhibitor increases the blocking ef cell mix. They find the two li fect, even though the inhibitor decreases gands act synergistically to polymer binding to the virus. The more prevent the virus from bind loosely bound polymer apparently better ing to the cells [Chem. Biol, 3,97 prevents the virus from adhering to the red blood cells. (1996)]. This synergism is brought about by the unfettering of the polymer at neuraminidase inhibitors of interactions between bio sites on the virus. logical surfaces. Their work opens the "The addition of the neuraminidase way to designing a new class of flu inhibitor enhances the ability of the drugs. polymer to stabilize the surface of the The new approach focuses on a syn virus sterically," says Mammen. thetic polyvalent polyacrylamide that In the presence of the neuramini binds to two proteins covering the sur dase inhibitor, the displaced polymer face of the flu virus. Most abundant is loops out from the virus. The loops of hemagglutinin, which binds to sugars the water-swollen polyacrylamide are called sialic acid that dot the surface of thought to increase the polymer's cells being attacked by the virus. The ability to stabilize the virus sterically other protein, neuraminidase, is an en and thus boost the polymer's inhibito zyme that cleaves sialic acid. Neura ry effect. minidase is thought to enable the virus "We have made an effective inhibi to chop its way through mucous secre tor of virus-cell attachment," says tions—which can be rich in sialic ac Mammen. "But a number of issues— id—on its path toward infection. The including bioavailability, toxicity, and enzyme also helps newly synthesized clearance [from the body]—need to be flu virus escape from infected cells and addressed before we can take the step infect other cells. toward designing drugs that could The polymer, synthesized earlier by treat influenza." chemistry professor George M. WhiteMairin Brennan
iW
MARCH 4,1996 C&EN
7
