News
Near-IR imaging of peptide synthesis Infrared analysis has not been used extensively for monitoring combinatorial syntheses. Chieu D. Tran and Marc Fischer of Marquette University hope that their near-IR multispectral imaging technique will change that. In this issue of Analytical Chemistry (p 2255), they demonstrate that near-IR multispectral imaging can be used to follow the reactions in solid-phase peptide synthesis. Their spectrometer is based on an acoustooptic tunable filter (AOTF) and an InGaAs focal plane array camera. The InGaAs detector operates over the spectral range 1.0-1.7 um, and it is more sensitive than InSb and HgCdTe array detectors, which also respond in this region. In addition, the InGaAs detector operates at room temperature, obviating the need for liquid nitrogen. The peptide synthesis takes place in an aluminumframereaction cell with glass microscope slides for windows. Tran and Fischer used this spectrometer to monitor solid-phase peptide synthesis on aminomethylstyrene resin beads. A 250-mg sample of the beads has 0.475 mmol of the amino group. The amino group generates a well-resolved peak at 1529 nm, which is not present in the spectra of methylene chloride and chloroform, the solvents that they used. As a test of this method's quantitative abilities, benzoyl chloride was reacted with the beads. As the reaction progressed, the peak at 1529 nm decreased, and a second peak at 1476 nm increased. The second peak is due to the amide bond formed between the amino group on the bead and the acid chloride group of the benzoyl chloride. As expected, the two absorbance bands changed linearly with the addition of up to 0.475 mmol of benzoyl chloride. Confident that the spectrometer could indeed be used to follow the course of a reaction, Tran and Fischer used the spectrometer to monitor the synthesis of peptides on the beads. The first peptide they synthesized was a trialanine, which required three steps—activation of the amino acid, the coupling reaction, and deprotection of the amino group. (Each amino acid was protected with Af-fluorenylmetiioxycarbonyl, also known as Fmoc.) After the first amino acid was added, a band appeared at 1483 nm and the band at 1529 nm practucally disappeared, indicating that the pling efficiency was close to 100%. Following deprotection of the amino acid, the 442 A
spectrum contained bands at both 1529 and 1483 nm because amino groups were generated. This cycle was repeated twice. The authors performed similar experiments with glycine and valine. The reactions in the single compartment cell demonstrate the feasibility of this approach. However, the true promise of the technique is in following multiple reactions simultaneously. To reach that goal, Tran has constructed a multicompartment cell that is fundamentally similar to the single compartment cell. The cell is divided into compartments with a rubberframeplaced between the aluminumframeand the windows. Each compartment has a pathlength of 5 mm. Tran says that the number of compartments in the cell is limited only by the ability to do high-precision machining and by the spatial resolution of the system, which, in the current optical configuration, is the pixel size (40 x 40 um). He belleves
that it should be possible to monitor reactions in a 96 x 96 array. The multicompartment cell was used to monitor the individual reactions of glycine, valine, and alanine simultaneously. By taking spectra every 20 min during the first 2 h of die coupling reaction, the relative reaction rates for the different amino acids could be determined. So far, Tran has only used the technique to follow the growth of peptides composed of a single amino acid. "Our next step is to show that we can use the multivariable method to identify peptides with different amino acid combinations," he says. "Then we will try to increase the number of compartments in the cell." In addition, he is working on a next-generation instrument, which includes an InSb detector and extends the spectral range to 3.3 um. The longer wavelengths could allow them to use the system to monitor the synthesis of other materials. Celia Henry
GOVERNMENT AND SOCIETY
Is winter coming for Eureka? A major Europe-wide research initiative begun 15 years ago must face major decisions about its future in the next few months following an independent review of its activities. Eureka was started with the aim of coordinating industrial high-tech research and development to boost the global competitiveness of European industry. The initiative's method involves the development of marketable products by bringing together researchers and manufacturersfromtwo or more countries. In the mid-1980s, the emphasis was mainly on big companies that were interested in carrying out strategically significant, long-term projects. Things have changed since then. Europe's political, economic, and commercial structure has undergone massive upheaval. Small- and medium-sized enterprises are filling niches once occupied by only the biggest multinationals, while the larger companies have concomitantly become increasingly decentralized. Eureka's portfolio of 718 completed projects adds up to an impressive investment of 12,299 million ECU (about $16 billion), with another 695 projects currently running that represent another 8221 million ECU ($11 billion). They involve some 3000 different organizations from 25
Analytical Chemistry News & Features, July 1, 1999
European countries and thus represent much more than the core European Community's 12 member states. One of the projects involves developing a software system for quantifying measurement uncertainty in analytical chemistry. Knowledge of measurement uncertainty is necessary for achieving traceability of chemical measurements to a recognized standard and for assessing results in the context of comparisons with legal limits or between products. Other projects cover medicine, biotechnology, new materials, environmental and atmospheric chemistry, and information technology. A formal assessment of Eureka in 1993 found that most companies involved expected to make new or improved products through Eureka, and 42% were anticipating moderate increases in sales; so it has not been without success. More recently, however, there has been disquiet among Eureka officials who worry that the initiative is not fulfilling its goals. Members also question whether the primary aim of opening strategic market advantages to European industry is being achieved. Now, an independent international panel chaired by Luke Georghiou, director of an advisory group called PREST (Policy Research in Engineering Science and Technology) at Manchester University, has carried out a strategic review of past and current
developments in the Eureka initiative. According to Georghiou, there is a clear role for Eureka in supporting the innovation needs of European industry, but only if the initiative is prepared to adapt, restructure, and attract new political commitment. Georghiou's group has suggested four possible scenarios: "autumn"—business-as-usual; "summer"—reorientation from R&D to innovation support and policy coordination; "spring"—relaunch and revitalization; and a fourth, "unthinkable" scenario, "winter" termination of Eureka. Officials have supported going ahead with the "spring" scenario, with a hint of "summer", but they have yet to action plan. The strategic review is currently making the rounds of European industry. First signs are that they support its conclusions. Ministers will decide what action to take at their conference in Istanbul at the end of June 1999. The pressure is on Germany, the incoming chair country, to ensure that Eureka faces a sunny future and does not perish in the depths of winter. David Bradley
Uniting peers An overhaul of the peer review of chemistry grant applications is in the cards at the U.K.'s scientific funding body, the Engineering and Physical Sciences Research Council (EPSRC). The aim is to experiment with a new system that will be more flexible and give interdisciplinary research a fairer hearing. According to Phil Burnell, manager of the EPSRC's chemistry program, "It has been said that the tail is wagging the dog, in the sense that prospective proposers often feel that they need to tailor their applications to fit the system." He adds that EPSRC wants to change that perception by creating a new flexible grant application structure that does not "shoehorn applications" into the traditional categories of organic, inorganic, and physical chemistry. The new idea will ensure that new proposals will be treated fairly. To this end, EPSRC, which was set up five years sgo, will lxperiment with a aingle-panel peer review system in September 1999. The system will run in parallel with the present three-panel setup. New proposals will be sent to both panels, and their decisions will be analyzed to see which method selects the best research most effectively. "We are still working on the details," Burnell explains. But why change the present system at
all? The reason for changing the system is that one can always tune things up to work better, Burnell explains. Some sections of the chemical community, such as those involved in instrumentation or those whose research overlaps divisions of chemistry, perceive they are not being best served by the present system. "Some good science may be choked off before it even gets written down on paper because the scientists feel it won't get a fair hearing," says Burnell. However, the main driving force behind the proposed changes is that the amount of cash allocated to a particular area is based on the number of proposals with no accounting for quality. "If one of the three current panels gets more applications, then it gets the lion's share of the funding, and I just don't think that'sright,"says Burnell. "Instead, money should follow the quality." The new system will mean that the funding structure will have less influence on the proposals that EPSRC attracts. "We are attempting to deal with proposals effectively, whatever their science content," he adds. Some members of the chemical community are worried that EPSRC is attempting a fait accompli to cut down on red tape. Nevertheless, following the single-panel experiment, EPSRC will consult the community to debate the issue openly before making afinaldecision. 'We should be reflecting what the eommunity wants to oo," says Burnell. The dog will then surely be wagging its tail. David Bradley
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Zare to receive Welch award Richard N. Zare, I I I I
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