New way to modify proteins developed - C&EN Global Enterprise

Publication Date: April 14, 1989. Copyright © 1989 American Chemical Society. ACS Chem. Eng. News Archives. Cite this:Chem. Eng. News 1989, 67, 16, X...
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it has been studied by physicists at millions of degrees. At those tem­ peratures, the D-D fusion reaction follows two major branches, one leading to the formation of tritium and a proton, and one leading to helium-3 and a neutron. Normally, both sets of products are produced about equally. But what if one or both of these branches is suppressed in room-temperature palladium? Measuring helium-3 might clarify the situation, but that is an extreme­ ly difficult measurement to make, Pons says. In one room-temperature fusion process—that catalyzed by massive particles called muons— scientists see no alteration of the branches. But then again, that fu­ sion process is not influenced by the presence of a metal matrix. Some scientists also speculate that D-D fusion in palladium may favor the formation of excited helium-4 nuclei. These particles might be able to transfer their excess energy to the palladium lattice, perhaps caus­ ing the observed overheating, Pons suggests. His group is now looking for helium-4 using mass spectrome­ try. Pons did not have to face his au­ dience's skepticism alone. As a lastminute addition to the program, the­ oretical chemist K. Birgitta Whaley of the University of California, Berkeley, offered some theoretical support for the Utah professor. She proposes that deuterons (deuterium nuclei), because of their "peculiar quantum characteristics/ 7 can facili­ tate the close approach of two deu­ terons, leading to quantum-mechan­ ical tunneling and fusion. Whaley notes that deuterons, unlike pro­ tons or tritium nuclei, are bosons (particles with a spin of 1). When bosons are squeezed together in­ side a metal lattice, she says, they exert a collective effect that screens out the repulsive Coulomb force that normally keeps deuterons apart. This screening allows them to approach one another and fuse more easily, she believes. Whaley says that this screening effect could also lead to cold fusion in deuterium-hydrogen, deuteriumtritium, and deuterium-lithium mixtures. In fact, Pons and other scientists are already investigating such reac­

tions as possible contributors to the unexplained heat excess. Tritium formed in the fusion cell, for exam­ ple, might undergo further fusion with a deuteron. And lithium also is a player because the Utah group is using lithium deuteroxide as the electrolyte. "We think lithium plays an important part in the process," Pons says. The chemical and physical state of the palladium electrode also ap­ pears to be an important factor. Pons notes that one out of 10 palladium samples in his lab "doesn't generate anything." And in the ones that do work, the fusion reaction doesn't become detectable until it has been charging for more than a week. Mahaffey's group at Georgia Tech, on the other hand, reports that fu­ sion begins almost immediately if the palladium electrode is first baked at 600 °C in a high vacuum. Of the five main speakers at the fusion symposium, Harold P. Furth, who directs Princeton University's Plasma Physics Laboratory, repre­ sented the fusion physics commu­ nity, which is the most skeptical of Pons' explanation. At a press con­ ference following the three-hour technical session, he carefully avoid­ ed giving his personal opinion on the cold fusion work. He did, how­ ever, say that additional experiments would have to be done before nu­ clear physicists could embrace the Utah findings. Crucial experiments to do, he says, include comparing the behavior of regular water and heavy water under the same elec­ trolytic conditions. Pons says he is preparing to do this. The practical applications of the new electrochemical process remain unclear because the process itself is not completely understood. But Pons says his group is pursuing scaleup to increase the energy output. Two other prominent electrochemists on the program, Allan J. Bard of the University of Texas, Austin, and Ernest B. Yeager of Case West­ ern Reserve University, seemed to be delighted with the attention elec­ trochemistry has been getting, par­ ticularly from physicists. "These have been exciting times for electrochemists," Yeager told the audience. "I hope your fusion fever stays high."

The symposium was organized through the tireless efforts of Valerie J. Kuck, a researcher at AT&T Bell Labs in Murray Hill, N.J. She was responsible for a similar last-minute special session on high-temperature superconductivity at the April 1987 ACS meeting, shortly after that field took off. Ron Dagani

New way to modify proteins developed Chemists at the University of Cali­ fornia, Berkeley, have developed a biosynthetic method for site-specific­ ally incorporating unnatural amino acids into proteins. Because the tech­ nique allows insertion of amino acids with novel steric and elec­ tronic properties, it is a potentially powerful new tool for studying pro­ tein structure and function. The new technique may allow chemists "to ask questions about pro­ teins never before thought possi­ b l e , " says Peter G. Schultz, the Berkeley associate chemistry profes­ sor who directed the research. The significance of the research, which was supported by the Office of Naval Research and the Depart­ ment of Energy, lies in the fact that only 20 natural amino acids are harnessed by living organisms to

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Schultz: tailor amino acid structures April 17, 1989 C&EN

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News of the Week build the diverse array of proteins fessor at Eidgenôssische Technische position encoded by TAG in a subfound in nature. Hochschule, Zurich, Switzerland. sequently synthesized protein. £. Recent advances in molecular bi- The unnatural amino acid is then coli, however, does not aminoacyology have revolutionized the study inserted into the position encoded late this particular yeast suppressor of proteins because researchers can by TAG by the protein-synthesizing tRNA. substitute any amino acid in a pro- machinery of Escherichia coli. Schultz and his coworkers suctein by one of the other 19 natural Using a semisynthetic yeast sup- cessfully replaced a phenylalanine amino acids. However, the range of pressor tRNA in an £. coli trans- residue in the enzyme ^-lactamase useful substitutions is limited. Few cription/translation system is im- with a number of unnatural amino substitutions that are sterically or portant, Schultz points out, because acids. One direction now being purfunctionally equivalent can be made tRNA molecules are recycled by sued by the chemists is to extend using the 20 natural amino acids. cells. If an E. coli suppressor tRNA the technique to other proteins. The "Ideally, one would like to tailor were used, the tRNA would be Berkeley chemists are also working the structure of an amino acid to reaminoacylated with a natural ami- to make the technique more effiaddress a specific structure-function no acid. This natural amino acid cient and easier to use. relationship/ 7 Schultz says. would then be inserted into the Rudy Baum There exist methods for incorporating unnatural amino acids into prochemical community ever since its teins, Schultz notes. These tech- FROM DALLAS discovery was claimed a few weeks niques, however, all suffer either ago by University of Utah's B. Stanley from nonselective incorporation of Pons and colleagues was captured the unnatural amino acid or size in a hastily arranged session during restrictions on the protein being the meeting. Held in the Dallas Consynthesized. vention Center's arena, more than The t e c h n i q u e , d e v e l o p e d by Although progress in a stunning 5000 people listened to Pons and Schultz and graduate students Christ- diversity of chemical fields was others discuss the unexpected reopher J. Noren, Spencer J. Anthony- reported last week at the American sults of his experiments and offer Cahill, and Michael C. Griffith, in- Chemical Society's 197th national theories to explain them (see page volves replacement of the three-base meeting in Dallas, attended by more 4). The special event, organized in DNA codon encoding the target than 9000, it was clearly nuclear fu- less than three weeks by Valerie J. amino acid with the "blank" non- sion that stole the show. However, Kuck, a researcher at AT&T Bell Labsense codon TAG (thymine-adenine- the excitement also filtered down oratories in Murray Hill, N.J., atguanine) [Science, 244, 183 (1989)]. to several other events, including a tracted immediate national attention. Under normal circumstances, the presidential plenary session on enMeanwhile, biotechnology drew messenger RNA carrying such a vironmental issues of biotechnolo- the spotlight of the presidential plenonsense codon would not be trans- gy, and a meeting of the ACS Coun- nary session. Organized by ACS lated into protein because no trans- cil, which decided to halt the long president Clayton F. Callis, the sesfer RNA (tRNA) carries the corre- string of annual increases in mem- sion kicked off a cluster of more sponding anticodon. than 100 papers on biotechnology bership dues, at least for a year. Schultz and his coworkers conThe excitement about cold nucle- presented in technical sessions at structed a semisynthetic version of ar fusion making the rounds in the the meeting. a n a t u r a l l y occurring molecule known as a suppressor tRNA that does possess the anticodon, using a method developed by Olke C. Uhlenbeck, a chemistry professor at University of Colorado, Boulder. In nature, this suppressor tRNA would carry one of the 20 natural amino acids and it would insert that amino acid into the position encoded by TAG, thus potentially suppressing the nonsense mutation. Instead, Schultz and coworkers chemically attach the unnatural amino acid of interest to their semisynthetic yeast suppressor tRNA, using modifications of methods developed independently by Sidney M. Hecht, a chemistry professor at the University of Virginia, Charlottesville, Presidential plenary session on biotechnology featured speakers (from left) and Josef Brunner, a chemistry pro- Carpenter, Kingsbury, Tiedje, and Callis

Fusion, biotechnology highlight ACS meeting

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April 17, 1989 C&EN