freezing points, or thermal hysteresis, indicates that the mechanism of antifreeze activity is a noncolligative one, according to Yin Yeh, professor of applied science, and Robert E. Feeney, emeritus professor, at the University of California, Davis [Chern. Rev., 96, 601 (1996)]. The term "antifreeze" should only be applied to proteins that function noncolligatively—that is, do not affect the melting point, Feeney tells C&EN. The synthesis reported by Nishimura and Tsuda "looks good," and the size of the AFGP "looks okay," he says. "But more data are needed on freezing and melting." The Japanese team points out that little evidence has been reported that can provide a complete explanation of antifreeze activity. Davies agrees. "Antifreezes like AFGP are thought to work by an adsorption-inhibition mechanism; that is, they bind to the surface of ice and inhibit its growth," he says. "The part of the mechanism that is least understood is the binding part." The AFGP synthesized by Tsuda and Nishimura is a useful size for investigating the mechanism of antifreeze activity, suggests Davies. "One potential application of facilitated glycopeptide synthesis would be to test the binding model by varying the disaccharide moiety," he says. However, this will require that the synthesis can be easily adapted to incorporate different sugars, he notes. Nishimura is confident this will be possible. "We can design a variety of antifreeze glycoprotein analogs by varying both the peptide sequence and the carbohydrate structures in order to investigate the mechanism of antifreeze activity by natural glycoproteins." The versatility of the synthetic strategy could also lead to other applications, according to Nishimura. The synthetic concept can be applied not only to the syntheses of natural antifreeze glycoproteins, but to the design of glycoclusters, with regulated distances between the sugar ligands, that are important in other biological systems.^
physics, materials science, combustion science, protein crystallization, and other research areas when experiments aren't influenced by gravity. The experiments were conducted in fall 1995 on the U.S. Microgravity Laboratory-2 (USML-2) and in spring 1996 on the U.S. Microgravity Platform-3 (USMP3). Many were continuations of earlier space research. "At the grassroots level, there's a lot of excitement" in microgravity research, said David M. Klaus, a research faculty member in aerospace engineering sciences at the University of Colorado, Boulder, and payload mission operations manager for BioServe Space Technologies. BioServe, a National Aeronautics & Space Administration Center for Space Commercialization, is affiliated with the University of Colorado and Kansas State University, Manhattan. Klaus discussed the effect of microgravity on brine shrimp, mammalian cells, viruses, protein crystals, plant seedlings, biomaterials, and microorganisms, among other items. "Most experiments are part of an ongoing study," he noted. Development of brine shrimp is accelerated significantly in space, he said, but the morphology of space- and Earthhatched shrimp is similar. The spacehatched shrimp have commercial potential as models for assessing toxicological effects, he explained. Klaus also described space research on osteoblasts (bone-forming cells) ultimately intended to lead to the development of pharmaceuticals that would counteract the loss of bone mass in astronauts. Bone tissue produced by chick osteoblasts grown in space appears to be less dense than that produced by Earthgrown control cells, he said. Space shuttle experiments have shown that microgravity inhibits the development of bone marrow macrophages, the cells that ingest foreign particles. Macrophages also respond to inflammation by stimulating B- and T-lymphocytes, the body's defense cells. Thus the findings in space could have applications in immunological research and drug development, said Klaus. Plants produce less lignin—the celluIntriguing results from laboratory experi- lose in their cell walls—in the absence of ments conducted in the ultra-low-gravity gravity. The energy they save could be reenvironment of space were presented at a directed to enhance the production of othconference last month that focused on er desirable metabolites, explained Klaus. two recent space shuttle missions. Speak- Space-grown plants also produce larger ers at the conference—held at the Nation- and heavier starch-storage vesicles "in an al Academy of Sciences in Washington, attempt to determine up from down," acD.C.—discussed insights gained into fluid cording to Jeffrey D. Smith, a research as-
Microgravity research looking up
Crystals ofi-alanine dehydrogenase grown in space (top) and on Earth (bottom).
sociate at NASA's Ames Research Center, Moffett Field, Calif. This finding is the "first evidence that plants physically adapt to a life in space by changing their sensitivity to gravity," Smith notes. Protein crystals grown in space often are superior to those grown on Earth, facilitating structure determination and rational drug design. But attempts to grow crystals aren't always successful. For example, several crystal-growth experiments were ruined by the delays in liftoff of the shuttle carrying USML-2. Despite the obstacles, a number of experiments on USML-2 went well, according to protein crystallographer Daniel C. Carter, president of New Century Pharmaceuticals, Huntsville, Ala. Among the successes he described were "the highest diffracting crystal and the largest crystal to date" of a DuPont Merck HIV protease complexed to a proprietary inhibitor, and "the best structure obtained over three flights" for human antithromMARCH 3, 1997 C&EN 37
science bin (a protease inhibitor that controls blood coagulation) provided by staictural biologist Mark R. Wardell at Washing ton University, St. Louis. DuPont Merck and Washington University researchers were among the coinvestigators from eight institutions that teamed up with Carter on the USML-2 experiments. Carter cautioned against judging results based on a single experiment. "An experi ment that doesn't fare well on one flight may be exemplary on another," he said. He noted that space research is hampered by the long intervals between flights. "Once we didn't get toflyfor 18 months," he said. "When you grow crystals on a dai ly basis, that has a big impact." Experiments on USMP-3 measured densi ty fluctuations in xenon near its critical point. The behavior of a material at its criti cal point is controlled by random fluctua tions in density that become macroscopic near the critical point. On Earth, the weight of afluidcompresses density so that most of a sample cannot be maintained at its critical point. In space, however, microgravity re duces thefluid'sweight and widens the crit ical volume, enabling researchers to make measurements. Xenon was chosen to mod el critical-point behavior because its critical temperature (Tc) of 16.7 °C is relatively close to ambient temperature. Understand ing how xenon behaves at its critical point can provide insight intofluids,glasses, mag nets, liquid crystals, and superconductors. The "Zeno" experiment, which uses a specially built precision-light-scattering spectrometer to monitor changes in the turbidity of a sample in a weightless envi ronment and to measure time correlations in the photons of light scattered, was first performed in March 1994 on USMP-2. "But we couldn't have known how to under stand the data from that flight without the data from the [USMP-3]flight,"said Robert W. Gammon, a professor of physics at the Institute for Physical Science & Technolo gy, University of Maryland, College Park. The scientists were able to calculate xe non's Tc to within 10 μΚ and measure temperature-imposed density fluctuations to within 100 μΚ of xenon's Tc. Matthew B. Koss, an assistant professor of materials science and engineering at Rensselaer Polytechnic Institute, Troy, N.Y., emphasized the importance of get ting results out quickly and obtaining feed back on other people's work so research ers will know "which question to pursue" on the next mission. At the conference, Koss described the effects of microgravity on denditritic patterns in metal alloys. Mairin Brennan 38 MARCH 3, 1997 C&EN
software/database
update
^ ISIS 2.1 (MDL Information Systems, pricing available from company, circle 301), for Windows and Macintosh, is software for registration, management, retrieval, display, and analysis of scientif ic data. This version provides enhanced capabilities for the representation, stor age, and management of polymer infor mation and also includes chemical repre sentation enhancements.
40% discount to academics and stu dents; circle 307), for the Power Macin tosh and Windows 3.1, 95, and NT computers, provides a range of facili ties to manage, analyze, and search chemical "objects" and associated data within the Microsoft Excel spreadsheet environment. Enhancements in this ver sion include faster chemical table opera tions and stereochemical searching.
• Scientific products (VWR Scien tific Products, circle 302) can now be ordered direct over the web at http:// www.vwrsp.com. The company mar kets laboratory chemicals, equipment, and supplies.
• Accord Chemistry Viewer (Syn opsys Scientific Systems, free, circle 308) for the Power Macintosh can be freely downloaded from Synopsys' web site (http://www.synopsys.co.uk/) for personal, academic, and registered cor porate use. Installed as a helper applica tion for web-browsers, it enables users to display chemical strucaires and reac tions downloaded from the web in a variety of chemical formats—including Accord, SMILES strings, ChemDraw files, Molfiles, and Rxnfiles. It also makes it possible to display structures received as MIME attachments to e-mail messages. The viewer is also available for Windows 3.1, 95, and NT.
• ChemPrep (Institute for Scientific Information, subscription price avail able from vendor, circle 303), a reac tion database on CD-ROM, is search able by substructure, transformation, or text. Data are available on over 300,000 reactions from 1986 to the present, and the database will be up dated quarterly. ChemPrep runs un der Windows 3.1. ^ Chart of the Nuclides: A Tutorial (Physics Academic Software, $100, circle 304), for Macintosh II or later computers, helps students learn how to read and understand data present ed in a standard chart of nuclides. ^ TRC Thermophysical Databank (Technical Database Services, pricing available from company, circle 305) provides evaluated chemical engineer ing data on thermodynamic, thermochemical, and transport properties of approximately 10,000 organic and nonmetallic inorganic compounds and their binary and ternary mixtures. Cur rently, data may be obtained by submit ting search requests via the Internet, phone, or fax, but the company plans to provide direct public access to the file in the fourth quarter of 1997.
• DMCplus (Aspen Technology, typical single-use license $70,000, cir cle 309) is a multivariable process controller for Windows 95 and NT and a variety of Digital, UNIX, and IBM systems. Process engineers use DMCplus to model, predict, and con trol process manufacturing. ^ FactorySuite and FactorySuite Plus (Wonderware; $9,950 and $12,500, respectively; circle 310) are industrial automation programs for Windows NT. FactorySuite provides process visualization, PC-based ma chine and process control, real-time plant data management, Internet/ intranet viewing, and factory equip ment interfacing. The Plus program adds work-in-progress tracking and production and batch management.
^ Chem-X/Inventory (Chemical De sign, price available from company, cir cle 306) is a module of the molecularmodeling program Chem-X that manag es reagent and screening-compound databases for combinatorial chemistry applications. It runs on a variety of plat forms, ranging from PCs and Macin toshes to client-server systems.
^ Chemkey Search (Heterodata, $475 single user, circle 311) is a data base of 50,000 references from organic chemistry journals with an emphasis on synthetic methodology, asymmetric synthesis, stereochemistry, and hetero cyclic and organometallic chemistry. A Macintosh- and PC-based program, it is updated yearly.
^ Accord for Excel 2.5 (Synopsys Scientific Systems; $695, $175 upgrade,
^ For information on these items, see Reader Service Card
