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NEWS OF THE WEEK NOBEL PRIZES: Merrifïeld wins chemistry award R. Bruce Merrifield, John D. Rocke- feller Jr. Professor at Rockefeller University in New York City, has been selected to receive the 1984 Nobel Prize in Chemistry. Merri- field, a protein biochemist, is being awarded the prize for his develop- ment in the early 1960s of a method of solid-phase synthesis of pep- tides. The Royal Swedish Academy of Sciences, which selects chemistry prizewinners, calls the technique "a completely new approach to or- ganic synthesis'' that has "brought about a revolution in peptide and protein chemistry" and led to the synthesis of thousands of different peptides. Merrifield's general prin- ciple also is used for synthesizing other biopolymers, particularly oligonucleotides, which are impor- tant in hybrid DNA research, the Swedish academy says. Before Merrifield's work, peptides were synthesized according to the method worked out by an earlier Nobel Prize winner, Emil Fischer. In his technique, the carboxylic acid group of one amino acid and the amino group of another were react- ed with protecting groups and the two nonprotected ends allowed to react with one another to form a peptide bond. This dipeptide was purified, one of its protective groups removed, and the entire unit re- acted with another partially blocked amino acid to produce a tripeptide. After many repetitions, a long-chain polypeptide could be built up. But the time involved and the loss of product in the repeated purifications required after each peptide bond synthesis put a practical limit of about eight or nine amino acid resi- dues in a peptide synthesized by this method. Merrifield attaches the first ami- no acid of his peptide chain through Merrifield: peptide synthesis method its carboxylic group to an insoluble polystyrene support. Thus, the prod- uct becomes part of a solid phase, and by-products and unreacted starting materials can be removed after each synthetic step by filtra- tion and washing of the polymer. Only when the entire synthesis is complete is the peptide removed from the solid support. The process is much faster, and, even more important, the yield in each indi- vidual step can be increased with this technique to 99.5% or better. By this method a peptide contain- ing 100 amino acid residues can be synthesized with an overall yield of 61%, compared with a theoretical yield in the neighborhood of 0.003% for the same synthesis without the solid support. Merrifield and his coworkers at Rockefeller have used the technique to synthesize several important pep- tides and proteins including brady- kinin, insulin, and ribonuclease. They also automated the technique, producing in 1965 the first work- ing model of an automatic peptide synthesizer. Peptide synthesis is now done routinely using commer- cially available automatic synthesiz- ers. A similar technique also has been applied to the synthesis of nu- cleic acid polymers, where auto- mated apparatus that can be pro- gramed to synthesize the desired product are now in wide use. "Al- though Merrifield has not worked in [the area of DNA synthesis] himself, it is clearly his ideas which have found a new application here," the Swedish academy says. This year's physics prize is to be awarded jointly to Carlo Rubbia, an Italian physicist who divides his time between the European Organi- zation for Nuclear Research (CERN) in Geneva and Harvard University, where he is professor of physics, and Simon Van der Meer, a Dutch engineer who also works at CERN. Rubbia and Van Der Meer will re- ceive the prize for "their decisive contributions to the large project which led to the discovery of the field particles W and Z, communica- tors of weak interaction," the Swed- ish academy says. Discovery of the W and Ζ parti- cles was announced only last year by Rubbia and large teams of collab- orators working with CERN's super- accelerator. It was Rubbia's idea in the mid-1970s to convert an existing large accelerator into a storage ring for protons and antiprotons, where head-on collisions between the stored particles could take place and W and Ζ particles, if they existed, might be detected. Van der Meer invented a method for densely pack- ing and storing protons and anti- 6 October 22, 1984 C&EN

NOBEL PRIZES: Merrifield wins chemistry award

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NEWS OF THE WEEK

NOBEL PRIZES: Merrifïeld wins chemistry award

R. Bruce Merrifield, John D. Rocke­feller Jr. Professor at Rockefeller University in New York City, has been selected to receive the 1984 Nobel Prize in Chemistry. Merri­field, a protein biochemist, is being awarded the prize for his develop­ment in the early 1960s of a method of solid-phase synthesis of pep­tides.

The Royal Swedish Academy of Sciences, which selects chemistry prizewinners, calls the technique "a completely new approach to or­ganic synthesis'' that has "brought about a revolution in peptide and protein chemistry" and led to the synthesis of thousands of different peptides. Merrifield's general prin­ciple also is used for synthesizing other b iopolymers , part icular ly oligonucleotides, which are impor­tant in hybrid DNA research, the Swedish academy says.

Before Merrifield's work, peptides were synthesized according to the method worked out by an earlier Nobel Prize winner, Emil Fischer. In his technique, the carboxylic acid group of one amino acid and the amino group of another were react­ed with protecting groups and the two nonprotected ends allowed to react with one another to form a peptide bond. This dipeptide was purified, one of its protective groups removed, and the entire unit re­acted with another partially blocked amino acid to produce a tripeptide. After many repetitions, a long-chain polypeptide could be built up. But the time involved and the loss of product in the repeated purifications required after each peptide bond synthesis put a practical limit of about eight or nine amino acid resi­dues in a peptide synthesized by this method.

Merrifield attaches the first ami­no acid of his peptide chain through

Merrifield: peptide synthesis method

its carboxylic group to an insoluble polystyrene support. Thus, the prod­uct becomes part of a solid phase, and by-products and unreacted starting materials can be removed after each synthetic step by filtra­tion and washing of the polymer. Only when the entire synthesis is complete is the peptide removed from the solid support. The process is much faster, and, even more important, the yield in each indi­vidual step can be increased with this technique to 99.5% or better. By this method a peptide contain­ing 100 amino acid residues can be synthesized with an overall yield of 61%, compared with a theoretical yield in the neighborhood of 0.003% for the same synthesis without the solid support.

Merrifield and his coworkers at Rockefeller have used the technique

to synthesize several important pep­tides and proteins including brady-kinin, insulin, and ribonuclease. They also automated the technique, producing in 1965 the first work­ing model of an automatic peptide synthesizer. Peptide synthesis is now done routinely using commer­cially available automatic synthesiz­ers. A similar technique also has been applied to the synthesis of nu­cleic acid polymers, where auto­mated apparatus that can be pro­gramed to synthesize the desired product are now in wide use. "Al­though Merrifield has not worked in [the area of DNA synthesis] himself, it is clearly his ideas which have found a new application here," the Swedish academy says.

This year's physics prize is to be awarded jointly to Carlo Rubbia, an Italian physicist who divides his time between the European Organi­zation for Nuclear Research (CERN) in Geneva and Harvard University, where he is professor of physics, and Simon Van der Meer, a Dutch engineer who also works at CERN. Rubbia and Van Der Meer will re­ceive the prize for "their decisive contributions to the large project which led to the discovery of the field particles W and Z, communica­tors of weak interaction," the Swed­ish academy says.

Discovery of the W and Ζ parti­cles was announced only last year by Rubbia and large teams of collab­orators working with CERN's super-accelerator. It was Rubbia's idea in the mid-1970s to convert an existing large accelerator into a storage ring for protons and antiprotons, where head-on collisions between the stored particles could take place and W and Ζ particles, if they existed, might be detected. Van der Meer invented a method for densely pack­ing and storing protons and anti-

6 October 22, 1984 C&EN

protons that made the collision ex­periments possible.

The Nobel Prize in Physiology or Medicine this year is divided three ways among theoretical immunolo-gist Niels K. Jerne, a Danish scien­tist who is professor emeritus of the Basel Institute of Immunology in Switzerland, Georges J. F. Kôhler, a West German immunologist, also at the Basel Institute, and Argentin­ean Cesar Milstein, who heads the division of protein and nucleic acid chemistry at Cambridge University in England.

According to the Karolinska Insti­tute, which selects the prizewinners in medicine, Jerne is the leading theoretician in immunology of the past 30 years. "In three main theo­ries, he has elucidated central is­sues concerning specificity, devel­opment and regulation of the im­mune system in a comprehensive and convincing way/ ' the institute says. "By his theories, Jerne has

Nobel science prizewinners ( clockwise from bottom left) Milstein, Jerne, and Kôhler

outlined the development of mod­ern immunology."

Kôhler and Milstein will receive their share of the prize for develop­ing in the mid-1970s a method to produce monoclonal, or identical, antibodies with predetermined speci­ficity using hybridoma cells. Their method, in which antibody-produc­ing cells are immortalized by fus­ing them with the tumor cells, al­lows unlimited production of mono­clonal antibodies with the predeter­mined specificity. It has opened up new avenues for detailed study of the immune system as well as new methods for characterizing diseases and treating them. Π

ACS election ballots mailed Ballots for this fall's ACS national election were mailed Oct. 4. If your ballot hasn't arrived yet, you may re­quest that a duplicate ballot be sent to you by calling the ACS Office of the Assistant Secretary (202) 872-4510 no later than Nov. 1. Deadline for receipt of all marked ballots at ACS headquarters in Washington, D.C., is Nov. 13.

U.S. urged to lead in tropospheric chemistry In what one science manager terms the "most imaginative report the National Science Academy has pro­duced / ' a panel of atmospheric chemists calls for the U.S. to take the lead in a global effort to under­stand the chemistry of the tropo­sphere—that part of the atmosphere in which humans live and pollute.

The panel, chaired by Robert A. Duce of the University of Rhode Island, is asking the nation to do something rather radical: commit scientific expertise for a long peri­od of time to a fundamental exer­cise that has no immediate payoff. But its plan for action spelled out in "Global Tropospheric Chemistry" is not just an intellectual exercise. As the panel's vice chairman Ralph Cicerone, head of the atmospheric chemistry division at the National Center for Atmospheric Chemistry, argues, the U.S. needs to extricate itself from the "crisis response mode" that has characterized its re­sponse to pollution problems of the past 15 years.

To do that, basic questions of how chemical systems of the biosphere— the land and oceans—interact with the chemistry of the troposphere, and in turn, how tropospheric chem­istry governs global temperature need to be answered. "We're not asking the U.S. government to walk away from pollution crises such as acid rain and the greenhouse effect. We, as a panel, are trying to lay the scientific framework to allow the U.S. and others to get ahead of these problems," Cicerone explains.

That framework would build a coordinated research effort to an­swer basic questions about processes controlling the chemistry of the troposphere. What mechanisms con­trol the input of trace chemicals to the troposphere? What controls the long-range transport and transfor­mation of these chemicals? And, ultimately, how are these substances removed from the troposphere?

To answer these questions, the global tropospheric chemistry pro­gram, as proposed, would evaluate biological sources of chemical sub­stances, determine the global distri-

October22, 1984 C&EN 7