Robert Bruce Merrifield
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Robert Bruce Merrifield
American biochemist (1921–
Born in Fort Worth, Texas, Merrifield was educated at the University of California, Los Angeles, where he received his PhD in 1949. He began work immediately at Rockefeller University, New York, and was appointed to the chair of biochemistry in 1966, a post he held until his retirement in 1992.
In the 1950s Merrifield began work on solid-phase peptide synthesis (SPPS). Peptides, like proteins, are composed of chains of amino acids, but have shorter and less complicated chains. Naturally occurring ones possess important physiological properties. The ability to synthesize peptides cheaply and quickly would lead to numerous commercial and medical gains. Yet the synthesis of a polypeptide using traditional methods could take many months.
In peptides the amine end (–NH2) of one amino acid reacts with the carboxyl end (–COOH) of another. To prepare a pure product of known structure, amino acids have to be coupled in a specific sequence. To achieve this the amine group on one amino acid and carboxyl group on the other must be blocked, so that the other two ends are the ones reacting. And this must be done as each further amino acid is added. In addition, at each stage the product must be isolated and purified. This will involve crystallizing the products. The synthesis of a hundred-unit peptide would involve ninety-nine such procedures. The need for improvement in the technique was painfully clear to peptide chemists.
Merrifield's innovation was to apply an ion-exchange technique by bonding the amino acids, one at a time, to an insoluble solid support. A polystyrene resin was the original choice. As the solid support was insoluble in the various solvents used, all the intermediate products and impurities could be simply washed away by using the appropriate reagent. Much initial work was required in setting up the right kinds of activating agents, blocking agents, and solvents. In 1964 in eight days Merrifield single-handedly synthesized bradykinin, a nine-amino-acid peptide that dilates blood vessels.
One further aspect of Merrifield's process is that it can be fully automated. To demonstrate the power and potential of his method Merrifield undertook in 1965 the automatic synthesis of insulin. With 51 amino acids and two peptide chains held together by two disulfide bridges, the molecule was a formidable challenge. Although more than 5000 operations were involved in assembling the chains, most of these were carried out automatically in a few days. The linking of the two chains, however, was achieved by more traditional methods. The resulting insulin was active in the standard biological assay.
For his development of the technique Merrifield was awarded the 1984 Nobel Prize for chemistry.
Merrifield, Robert Bruce, 1921-2006, American chemist, b. Fort Worth, Tex., Ph.D. Univ. of California at Los Angeles, 1949. As a researcher at the Rockefeller Institute for Medical Research (later Rockefeller Univ.), with which he was associated until his death, Merrifield developed a comparatively simple method for synthesizing polypeptides. The innovation, which won Merrifield the 1984 Nobel Prize in Chemistry, greatly facilitated the manufacture of insulin, interferon, and other drugs.
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Mer·ri·field
(mĕr'ə-fēld'), R(obert) Bruce Born 1921.
American biochemist. He won a 1984 Nobel Prize for developing a method of synthesizing peptides and proteins from amino acids.
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Robert Bruce Merrifield
| Robert Bruce Merrifield | |
|---|---|
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| Born | July 15, 1921 Fort Worth, Texas |
| Died | May 14, 2006 (aged 84) Cresskill, New Jersey |
| Nationality | United States |
| Fields | biochemistry |
| Known for | solid phase peptide synthesis |
| Notable awards | Nobel Prize in Chemistry in 1984 |
Robert Bruce Merrifield (July 15, 1921 – May 14, 2006) was an American biochemist who won the Nobel Prize in Chemistry in 1984 for the invention of solid phase peptide synthesis.[1]
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Early life
He was born in Fort Worth, Texas, on 15 July 1921, the only son of George E. Merrifield and Lorene née Lucas. In 1923 the family moved to California where he attended nine grade schools and two high schools before graduating from Montebello High School in 1939. It was there that he developed an interest both in chemistry and in astronomy.
After two years at Pasadena Junior College he transferred to the University of California at Los Angeles (UCLA). After graduation in chemistry he worked for a year at the Philip R. Park Research Foundation taking care of an animal colony and assisting with growth experiments on synthetic amino acid diets. One of these was the experiment by Geiger that first demonstrated that the essential amino acids must be present simultaneously for growth to occur.
He returned to graduate school at the UCLA chemistry department with professor of biochemistry M.S. Dunn to develop microbiological methods for the quantitation of the pyrimidines. The day after graduating on 19 June 1949, he married Elizabeth Furlong and the next day left for New York City and the Rockefeller Institute for Medical Research.
Career
At the Institute, later Rockefeller University, he worked as an Assistant for Dr. D.W. Woolley on a dinucleotide growth factor he discovered in graduate school and on peptide growth factors that Woolley had discovered earlier. These studies led to the need for peptide synthesis and, eventually, to the idea for solid phase peptide synthesis (SPPS) in 1959. In 1963, he was sole author of a classic paper in the Journal of the American Chemical Society in which he reported a method he called solid phase peptide synthesis, which is the fifth most cited paper in the journal's history.[2]
In the mid-60s Dr. Merrifield's laboratory first synthesized bradykinin, angiotensin, desamino-oxytocin and insulin. In 1969, he and his colleague Bernd Gutte announced the first synthesis of the enzyme, ribonuclease A. This work proved the chemical nature of enzymes. [3] [4][5][6][7][8]
Dr. Merrifield's method greatly stimulated progress in biochemistry, pharmacology and medicine, making possible the systematic exploration of the structural bases of the activities of enzymes, hormones and antibodies. The development and applications of the technique continued to occupy his laboratory, where he remained active at the bench until recently. In 1993, he published his autobiography, "Life during a Golden Age of Peptide Chemistry." He received the Association of Biomolecular Resource Facilities Award for outstanding contributions to Biomolecular Technologies in 1998.
SPPS was subsequently used to synthesize ribonuclease A (with Bernd Gutte). This achievement was all the more significant in that it demonstrated that the linear sequence of amino acids joined in peptide bonds determined directly the tertiary structure of a peptide or protein. I.e. that information coded in one dimension can directly determine the three dimensional structure of a molecule.
SPPS has been expanded to include solid phase synthesis of nucleotides and saccharides.
Personal life
After raising their six children, James, Nancy, Betsy, Cathy, Laurie and Sally, his wife Elizabeth (Libby), a biologist by training, joined the Merrifield laboratory at Rockefeller University where she worked for over 23 years.
After a long illness R. Bruce Merrifield died on May 14, 2006 at the age of 84 in his home in Cresskill, New Jersey.[9] He is survived by his wife, children and 16 grandchildren.
References
- ^ Kenneth Chang (2006-05-06). "R. Bruce Merrifield, Who Won Nobel Prize in Chemistry, Dies at 84". The New York Times. http://www.nytimes.com/2006/05/20/nyregion/20merrifield.html. Retrieved 2008-04-12.
- ^ R. B. Merrifield (1963), "Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide", Journal of the American Chemical Society 85 (14): 2149, doi:10.1021/ja00897a025.
- ^ Jones, John H (2007), "R.B. Merrifield: European footnotes to his life and work", Journal of Peptide Science 13 (6): 363–7, 2007 Jun, doi:10.1002/psc.857, PMID 17516587
- ^ Gierasch, Lila M (2006), "Editorial: Passing of a gentle giant of peptide science: in memoriam, R. Bruce Merrifield", Biopolymers 84 (5): 433–4, doi:10.1002/bip.20574, PMID 16850497
- ^ Lerner, Richard A (2006), "Retrospective. R. Bruce Merrifield (1921-2006)", Science 313 (5783): 57, 2006 Jul 7, doi:10.1126/science.1130957, PMID 16825560
- ^ Sano, S (1985), "[Work of Dr. Robert Merrifield, with special reference to the development of solid phase peptide synthesis]", Tanpakushitsu Kakusan Koso 30 (1): 51–3, 1985 Jan, PMID 3883428
- ^ Domagk, G F (1984), "[The 1984 Nobel prize for chemistry. Synthetic hormones and enzymes with Merrifield's peptide synthesizer]", Dtsch. Med. Wochenschr. 109 (49): 1901–2, 1984 Dec 7, PMID 6389076
- ^ "Nobel Prize biography of Bruce Merrifield". http://nobelprize.org/chemistry/laureates/1984/merrifield-bio.html.
- ^ Petkewich, Rachel. "Nobel Laureate R. Bruce Merrifield Dies At 84", Chemical & Engineering News, May 23, 2006. Accessed May 9, 2007. "Robert Bruce Merrifield, a biochemist who won the 1984 Nobel Prize in Chemistry for a method he named solid-phase peptide synthesis, died on May 14 at his home in Cresskill, N.J., after a long illness. He was 84."
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