SCIENCE/TECHNOLOGY lography provide that information, albeit at considerable difficulty and expense. The three new computational methods do not. Nevertheless, the new programs represent a key advance in that "the number of proteins predicted per parameter has now been stepped up by 100-fold or 1,000-fold," says Dill. The computational models of the past have each been "a good 'first step/ succeeding at some level, but not improvable beyond that. So it has never been clear how to fix what is broken. The problem is that with hundreds of parameters, if the model fails to predict some protein structures, how do you systematically proceed to improve them? There are too many." The new methods "do not yet solve the protein-folding problem," he concedes. "But with their far fewer parameters, these new models now promise to allow us to progress to the 'second step' and 'third step/ toward a systematic development of better and better protein-folding algorithms." Q
me
National Industrial Competitiveness through
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• GRANTS AVAILABLE to promote energy efficiency, clean production, and economic competitiveness in industry • Apply through your state energy, pollution prevention, or business development office • Cost share: 45% federal-55% industry/state • The FY 1996 solicitation period opens November 1,1995 and closes January 16,1996 • For more information: — cali:1-800-DOE-EREC — Hearing impaired 1-800-273-2957 — internet: http://www.nrel.gov/documents/ nice3/nice-3.htmi • To request a copy of the grant application — fax your name, company, address, and phone number to: NICE3Soliciation Request 703-893-0400 U.S. Department of Energy Office of Energy Efficiency and Renewable Energy Office of industrial Technologies and Office of Technical and Financial Assistance CIRCLE 9 ON READER SERVICE CARD
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NOVEMBER 6,1995 C&EN
Fully phosphorylated membrane anchor made Scientists at Duke University have synthesized for the first time the fully phosphorylated membrane anchor of a glycoprotein. The work provides access to compounds that could prove to be invaluable tools for biochemists and cell biologists investigating the functions of glycophosphatidylinositol (GPI) anchors. GPI membrane anchors are glycolipids that link proteins to cell membranes. Discovered fairly recently, GPIs appear to mediate a wide range of biological responses. However, the Anchor (red) links a glycoprotein (yellow and blue) minuscule amounts available to a cell-surface membrane (green). from natural sources have been a barrier to full elaboration of their bio- will allow researchers to study this comlogical role. The new synthetic work of plex process more closely. chemistry professor Bertram O. FraserThe Duke team began with a hepReid and his former postdoctoral fel- tasaccharide with sites for future phoslow A. Stewart Campbell eliminates phorylations protected. Their "masterful this barrier [/. Am. Chem. Soc, 117, orchestration of selective protections and 10387 (1995)]. deprotections" is a major achievement in In 1993, Fraser-Reid and other Duke carbohydrate synthesis, says Samuel J. coworkers prepared an unphosphory- Danishefsky of the Memorial Sloan-Ketlated membrane anchor (C&EN, Aug. tering Cancer Center, New York City, 30, 1993, page 20). This latest work de- and Columbia University. The synthesis involved a lot of intelliscribes how the phosphate groups can gent guesswork, because complex oligobe put in place. "The phosphate groups are essential// saccharides "fold on top of themselves explains Fraser-Reid. "The anchor is not and they coil and they interact in unprejust there to hold the protein. It's a con- dictable ways," Fraser-Reid says. "For a duit for the message. And the phos- long time, Campbell was going only on phates are the 'spark plugs' that set off his instincts, which were superb." GPI anchors are ubiquitous in euthe chain of events" leading to, for exkaryotic cells. The pentasaccharide ample, regulation of glucose levels. "This successful synthesis will go a backbone is conserved from protozolong way in clarifying and refining the ans to humans. The compound synthefield of GPI bioactivity," says Louis sized by the Duke team is a mammaliSchofield, an immunologist at the Walter an anchor. Compared with anchors from lower & Eliza Hall Institute of Medical Research, Melbourne, Australia. Schofield eukaryotes such as protozoans and has been studying signal transduction yeast, mammalian anchors have an exby GPI molecules. Recently, he showed tra phosphorylated mannose group. that these molecules activate signaling Thus, mammalian anchors have three pathways that trigger a host of intracel- phosphate groups, whereas those from lular responses leading to activation of lower eukaryotes have only two. The Duke team "must be commended for the immune system. GPI-anchored proteins have been achieving the addition of this key subimplicated in the movement of signals stituent," says Ferguson. "It would appear that the third phosacross cell membranes, says biochemistry professor Michael A. J. Ferguson of phate is an evolutionary developthe University of Dundee, Scotland, ment," says Fraser-Reid. "One of the who led the team that reported the first questions that has to be settled is structure of a GPI membrane anchor in whether it does anything." Maureen Rouhi 1988. Access to synthetic compounds
