Two unique toxins characterized - C&EN Global Enterprise (ACS

Jul 6, 1981 - Toxic components of that venom, including a paralysis-causing protein called gilatoxin, now have been purified and partly characterized ...
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Science theorists. One trend cited by several speakers was closer liaison between theorists and experimenters. One speaker who fits in both camps at once is Thomas F. George of the University of Rochester. One particular place where closer cooperation is required is in the area of laser-induced collisions, George noted. Matter-radiation field interactions appear to be more significant than previously suspected. There is the important probability that totally unexpected products can be obtained from fieldfree experiments, implying new synthetic routes. George and his associates are engaged in basic investigations into field-free effects as well as into the activated state. George suggests that the transition state in collision dynamics may be a kind of shape resonance between several electronic states, one representing bound nuclear motion and the rest containing other reaction channels, A reaction involving such resonance, in principle, could be modified selectively by laser radiation, provided the activated complex survives long enough to absorb a photon. The laser is also useful in examining the roles of charged particles in collisions.

In this application it serves as a probe in interpreting emission spectra of reaction intermediates, and has led to the new field of laser photochemistry. One problem associated with the computing capacity now available to theorists is that the highly sophisticated mathematics involved sometimes obscures the underlying physics. One way around this problem is the "simplifying assumption." For example, for calculating potential energy surfaces for molecular species, one convenient approach is treating a polyatomic molecule as though it were a combination of diatomic fragments, which are easier to handle. The potential energies of the fragments are then mathematically "massaged" by the computer to yield the approximate energy surface of the polyatomic molecules. At least in the academic context, several observers suggested, the chemical engineer is becoming more and more the "approximator" in the newly unfolding arts and sciences surrounding the chemical dynamics of the molecular beam and the laser. Joseph Haggin, Chicago

tions, Tu prefers to stick with venoms from U.S. or at least North American creatures. "For some reason, most scientists have looked at non-U.S. toxins and have totally neglected the U.S. toxins," he says. "That's really bad." Thus, he and his coworkers also have studied venoms from other locally indigenous animals, particularly various rattlesnakes. The only noteworthy exception to this observance has been a study of venom from a sea snake found in Central America and in Asia. And the Colorado researchers pay for this exception, so to speak, by having to "collect the venom on our own," Tu says. Collecting specimens of Pacific gorgonians presumably is not only less hazardous but also less of a hardship, owing to the territory in which these creatures are found. Gorgonians were collected initially for testing on board the research ship, Alpha Helix, which dutifully plied the seas on this particular expedition from California southward to Panama Bay, hunting for pharmacologically active fauna. The ship is well-enough equipped to permit preliminary chemical and biological analysis on board—a research practice that might kindle interest in toxins in even the most timid individuals. The toxins of the two species of Two unique toxins characterized Gila monsters are both acidic proteins Two more representatives from na- The organism occupies a tropical and containing similar amino acid maketure's bountiful supply of deadly subtropical watery habitat off the ups, as well as having many similar toxins recently have been character- coast of Mexico. Fittingly, chemis- physical properties, such as size and ized. The two molecules, one a protein try-oriented oceanographers have immunological reactivities. The proand the other a diterpenoid, typify been studying the toxin. Among the tein toxins have molecular weights of the fiendishly diverse chemical oceanographers are William H. Fen- about 35,000 daltons, according to the weaponry that various organisms ical, Roy K. Okuda, and Maury M. Colorado State University biochemhave developed to ensure their own Bandurraga at the Scripps Institution ists. survival by poisoning their natural of Oceanography in La Jolla, Calif., The gila toxins apparently lack along with Paul Culver and Robert S. enzymic activity, or at least any of the enemies. The Gila monster looks like a Jacobs of the University of California, catalytic activities often linked with miniature leftover from the age of Santa Barbara [Science, 212, 1512 toxins from poisonous snakes and dinosaurs. It occupies a bleak desert (1981)]. Their main support is from other animals, Tu says. Some of those habitat in parts of the southwestern the National Oceanographic & At- enzymes include phospholipases (that is, enzymes that degrade phosphoU.S. and in Mexico, and belongs to mospheric Administration. the only genus of lizards that can Hendon and Tu call gilatoxin "a lipids, which help make up many make and secrete a deadly venom. new type, different from the well- kinds of cell membranes), and also Toxic components of that venom, characterized toxins of snakes, scor- proteins with hemorrhagic and heincluding a paralysis-causing protein pions, spiders, and bees." The two molytic activities. called gilatoxin, now have been puri- biochemists have studied toxins from Gilatoxin is considerably less pofied and partly characterized by bio- two closely related species of lizard, tent than comparable toxins from chemists Anthony T. Tu and Robert Heloderma suspectum and Helo- snakes, Tu says. He estimates that A. Hendon at Colorado State Uni- derma horridum. The venoms of the pure toxin is about 20- to 30-fold versity, Fort Collins [Biochemistry, these two lizards, one a U.S. species less potent than rattlesnake toxin, for 20, 3517 (1981)]. Their research sup- and the other from Mexico, are example. The LD50, the amount of port comes from the National Insti- available commercially. However, Tu pure toxin it takes to kill healthy mice tutes of Health. laments the expense and intermittent on average, is 2.5 mg per kg body Another recently characterized scarcity of the crude venoms, noting weight. natural toxin also works by paralyzing that each costs about $600 per gram "We don't know anything about victims, although apparently by dif- and that research progress sometimes the mechanism of action" of the ferent means. It is called lophotoxin, was interrupted when he and his col- gilatoxins, Tu says. Experiments to named for the Pacific sea whip of the league "used up all the U.S. supply." test mechanisms are only just begingenus Lophogorgia that produces it. Despite such occasional frustra- ning. However, because the toxin 24

C&EN July 6, 1981

Lophotoxin, a sea whip neuromuscular toxin /CHO

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