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Home , Adolf Windaus, Amanita virosa, Carnosine, Emil Abderhalden, Erik Jorpes, Franz Hofmeister

Appendix

In this Appendix biographical sketches are compiled of many scientists who have made notable contributions to the development of up to its present state. We have tried to consider names mainly connected with important events during the earlier periods of peptide history, but could not include all authors mentioned in the text of this book. This is particularly true for the more recent decades when the number of peptide and biologists increased to such an extent that their enumeration would have gone beyond the scope of this Appendix. 250 Appendix

Plate 8. Emil Abderhalden (1877-1950), Photo Plate 9. S. Akabori Leopoldina, Halle

J

Plate 10. Ernst Plate 11. Karel Blaha (1926-1988) Appendix 251

Plate 12. Max Brenner Plate 13. Hans Brockmann (1903-1988)

Plate 14. Victor Bruckner (1900- 1980) Plate 15. Pehr V. Edman (1916- 1977) 252 Appendix

Plate 16. Lyman C. Craig (1906-1974)

Plate 17. Vittorio Erspamer Plate 18. Joseph S. Fruton, Biochemist and Historian Appendix 253

Plate 19. Rolf Geiger (1923-1988) Plate 20. Wolfgang Konig

Plate 21. Dorothy Hodgkins Plate. 22. Franz Hofmeister (1850-1922), (Fischer, biograph. Lexikon) 254 Appendix

Plate 23. The picture shows the late Professor 1.E. Jorpes (r.j and Professor V. Mutt during their favorite pastime in the archipelago on the Baltic near

Plate 24. Ephraim Katchalski (Katzir) Plate 25. Abraham Patchornik Appendix 255

Plate 26. P.G. Katsoyannis Plate 27. George W. Kenner (1922-1978)

Plate 28. Edger Lederer (1908- 1988) Plate 29. Hennann Leuchs (1879-1945) 256 Appendix

Plate 30. Choh Hao Li (1913-1987) Plate 31. A.J.P. Martin

Plate 32. Miguel A. Ondetti Plate 33. Yuri A. Ovchinnikov (1934- 1988) Appendix 257

Plate 34. , 40 years a-Helix "We have now used this information (about interatomic distances, bond angles and other ... [the author]) to construct two reason• able hydrogen-bonded helical configurations for the polypeptide chain; we think that it is likely that these configurations constitute an impor• tant part of the structure of both fibrous and globular , as well as of synthetic poly• ". (From Linus Pauling, Robert B. Corey and H.R. Branson, The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain, Proc. NatL Acad. Sci. USA 37: 205-211, 1951)

Plate 35. Iphigenia Ph otaki (1921-1983) with 258 Appendix

Plate 36. H. Norman Rydon Plate 37. Shumpei Sakakibara

Plate 38. Plate 39. Robert Schwyzer Appendix 259

Plate 40. Ernesto ScofTone Plate 41. John C. Sheehan

Plate 42. M.M. Shemyakin Plate 43. Tetsuo Shiba 260 Appendix

Plate 44. R.L.M. Synge Plate 45. Emil Taschner (1900-1982)

Plate 46. Wang Yu Plate 47. Friedrich Wessely von Kamegg (1897-1967) (Courtesy Prof. K. Schliigl) Appendix 261

Plate 48. Friedrich Weygand (1911-1969) Plate 49. Bernhard Witkop

Plate 50. Robert B. Wordward Plate 51. Erich Wunsch 262 Appendix

Plate 52. Haruaki Yajima Plae 53. Geoffrey T. Young

Plate 54. The group of (Photo M. Forschelen, ) from left: H. Bremer, O. Brinkhoff, H. Zahn, R. Zabel, E. Schnabel, J. Meienhofer Appendix 263

Plate 55. Leonidas Zervas (1902-1980) at the age of about 60 264 Appendix

Abderhalden. Emil, 1877-1950 (p. 34, Plate 8) born in Oberuzwil, , studied medicine in where he graduated as M.D. in 1902. In the same year he moved to to join , where he combined chemistry with enzymology (p. 35). In 1908, he was appointed Professor of Physiological Chemistry at the School of Veterinary Medicine in Berlin. In 1911 he became Professor and Head of the Institute of of the University of Halle/Saale where he worked on the physiology and of pep tides, proteins and enzymes. Abderhalden was President of the "Deutsche Akademie der Naturforscher Leopoldina" from 1931 until 1945, the year in which he and his family were moved to West by American troops. He died in 1950 in Ziirich, Switzerland.

Akabori, Shiro (p. 116, Plate 9) born in Shizuoka Prefecture, Japan, in 1900, graduated from Tohoku Imperial University in 1925, research associate in the laboratory of Prof. Toshiyuki Majima and received his Doctor of Science degree from the same university in 1931. He studied in the laboratory of Prof. E. Waldschmidt-Leitz in the German University at Prague, Czechoslovakia from 1932 to 1934, appointed as Assistant Professor at Osaka Imperial University in 1935 where he advanced to full Professor (1939), Dean of the Faculty of Science (1947), and the President (1969). He established the Insitute for Research at Osaka University and served as the first Director of the Insitute (1957). Since retiring from Osaka University (1965), he has been the President and a trustee of the Protein Research Foundation to which the Peptide Institute belongs. He is a member of the Japanese Academy, and a member of numerous foreign Academies.

Bayer. Ernst (pp. 54, 234, Plate 10) born in 1927 in Ludwigshafen/Rhine, studied chemistry in Heidelberg, FreiburgfBr. Dr. rer. nat. 1954, from 1958 at the Technical University, Karlsruhe and University of Tiibingen, there associate professor in 1962, full professor in 1965.

Bergmann. Max, 1886-1944 (p. 45, Plate 3) born in 1886 in Fiirth, , begun studies of botany at the Technical Highschool in Munich, transferred to chemistry in E. Fischers laboratory in Berlin, where he worked on his doctoral thesis, 1911. Fischer engaged him as assistant in his personal laboratory to work in the field of, among other topics, amino acids and peptides. In 1920 he was appointed Acting Director at the Kaiser-Wilhelm-Institute for Fiber Research in Berlin-Dahlem. In 1922 he moved to Dresden as Director of the Kaiser-Wilhelm-Institute for Leather Research, where he, with Leonidas Zervas, invented the benzyloxycarbonyl group for the reversible protection of amino groups (p. 46). In 1934, Bergmann had to leave Nazi Germany. He was kindly received by the Rockefeller Institute for Medical Research in , where he successfully continued his investigations of amino acids and peptides with excellent collaborators (S. Moore, E. Stein et al.) (see p. 50) Bergmann died in 1944,58 years old, after a long illness in New York.

Biemann. Klaus (p. 128) born in Innsbruck, in 1926. He studied chemistry at his home Univ., and received his PhD in 1951. He was instructor of chemistry there until 1955 when he became Professor of Chemistry at the Massachusetts Institute of Technology, USA and has applied mass spectrometIY. in his investigations since then.

Blaha. Karel, 1926-1987 (pp. 122,231, Plate ll)was born in 1926 near Pilsen, Bohemia. In 1949, after graduating in chemistry at the Technical University in Prague, he joined -the Laboratory of Heterocyclic compounds led by Rudolf Lukes where he worked and gained experience of in depth. In 1960, Blaha went to the Institute of Organic Chemistry and Biochemistry of the Czechoslovak Academy of Sciences, and started his successful research in peptide chemistry, at first as a coworker of Joseph Rudinger, and after Rudinger's emigration (1968) his successor as Head of the Department.

Bodanszky, Miklos born in 1915 in Budapest, Hungary, received his doctorate at the Technical University of Budapest. After a few years in the pharmaceutical industry he was appointed as Head of the natural products department of the Institute for Medical Research and at the time became a lecturer in at the Technical University of Budapest. His work on active esters Appendix 265 started in this period (p.85). In 1956, he left Hungary and joined V. du Vigneaud, at Medical School in New York City. Here he demonstrated the stepwise strategy in a novel synthesis of . In 1959 he joined the Squibb Institute for Medical Research, where with his coworkers (among them Miguel A. Ondetti) he reported the first synthesis of the gastrointestinal hormone (p. 167). From 1966 until his retirement in 1983 he was professor of Chemistry and Biochemistry at Case Western Reserve University in Cleveland, Ohio.

Brenner, Max (pp. 58, 197,242, Plate 12) born in 1915 in Chur, Switzerland. Studied chemistry at the Technical University, Zurich, Diploma Chemical Ing. in 1937, Dr. Sc. techno after thesis with L. Ruzicka. Thereafter one year working at Rockefeller Institute in New York with on synthetic substrates for proteases, 1941-1947 research in the pharmaceutical-chemical industry, 1947 assistant to T. Reichstein, 1949 Lecturer, 1954 Professor until 1980 at the .

Brockmann, Hans, 1902-1988 (p. 118, Plate 13) born in 1903 in Altkloster near Hamburg, received his Dr. degree at the Univ. of HallejSaale (with E. Abderhalden, in 1930, went to at the Kaiser-Wilhelm (later Max-Planck)-Institute for Medical Research in Heidelberg where he did pioneering work on , e.g. of carotenoids. In 1935 he became Head of the biochemical department of the Chemistry Institute of the Univ. of Gottingen (Director ), in 1941 Prof. at the Univ. Posen, and after the war, in 1945, successor of A. Windaus in Gottingen until retirement in 1972. Antibiotica (actinomycin, p. 224 etc) ionophores (valinomycin, p. 201).

Bruckner, Viktor, 1900-1980 (pp. 41,236, Plate 14). Born in 1900 in Kesmark a small Carpathian town, graduated from the Technical University in Budapest, thereafter studied with Alexander Schonberg (Berlin) and (), then with Albert von Szent-Gyorgyi in Szeged (Hungary). Engaged in peptide chemistry from 1937 (bacterial capsular substances), in 1950 appointed as Director of the Institute of Organic Chemistry of the Eotvos Lorand University in Budapest. Died in Budapest in 1980.

Craig, Lyman C, 1906-1974(p. 55, Plate 16) son ofa farmer, was born in Palmyra, Iowa. In 1932, with a fresh Ph.D. degree from the University ofIowa at Ames, he moved to Baltimore to work at the as a National Research Council fellow. Two years later Craig joined the Rockefeller Institute in New York City to collaborate with A. Jacobs on the structure-elucidation of . Here he developed the fractionation of mixtures by repeated extraction procedures. Countercurrent distribution (CCD) turned out to be of great value in the isolation of natural and synthetic products. The definitive determination of the molecular weight of insulin, for instance, became possible through the isolation of the least substituted derivative by CCD. For the concentration of solutions recovered from CCD, he invented the rotary evaporator. Lyman C. Craig remained at the Rockefeller Institute during his entire career and was appointed Professor when the Institute became a University. His work was recognized by numerous awards. He died in 1974.

Curtius, Theodor, 1857-1928 (p. 25, Plate 2) born in Duisburg (Rhineland). He first studied music and natural sciences in Leipzig until 1876, and went after his military service in 1878 to Heidelberg to study chemistry with Robert Bunsen. He returned to Leipzig where he received his Ph.D. degree after a thesis guided by Hermann Kolbe in 1882 (first synthesis of a peptide, p. 26), moved to the University of Munich (A. Baeyer), where he was assistant from 1884-1886. In 1886 he graduated Dr. habil. at the University of Erlangen, in 1889 he moved as full professor to the University of Kiel. A call in 1892 to the University of Wurzburg as successor to Emil Fischer was not accepted, but he succeeded A.V. Kekule in Bonn in 1897, although for only one year until 1898 when he succeeded Victor Meyer at the University of Heidelberg as Head of the Chemical Institute. There he worked until the end of his life in 1928.

du Vigneaud, Vincent. See biography on pp. 153-155. 266 Appendix

Edman. Pehr Victor, 1916-1977 (pp. 118,240, Plate 15) born in Stockholm in 1916, matriculation examination in 1935, studied medicine at the Medical School in Stockholm from 1935, Bachelor of Medicine in 1938, graduation as a physician in 1946. Concurrently with his studies in medicine he started his training in biochemistry with Erik Jorpes. for a short time also with , and soon started a project on that led to a MD thesis. Then he widened his experience in protein chemistry during one year at the Rockefeller Institute in Princeton with Northrop and Kunitz (crystallization of proteolytic enzymes). On his return to , Edman was awarded an associate professorship in Lund in 1947 where he conducted his stepwise peptide degradation work (p. 118) between 1950 and 1956. In 1957 Pehr Edman accepted an otTer to be Director of Research at St. Vincent's School of Medical Research in Melbourne, Australia, where he remained for 15 years, during which the work on an automated sequence analyzer was finished in 1967. From 1972 until his death from a brain tumor in 1977 he was Director of the Department of Protein Chemistry of the Max-Planck-Institute for Biochemistry in Martinsried near Munich.

Erspamer. Vittorio (pp. 134,238, Plate 17), born in Malosco (Trento, ) in 1909, studied Medicine at the University of Padua (M.D. in 1939), was there assistant at the Institute of Comparative and Physiology from 1935-1938, then postdoctoral fellow at the Universities of Berlin and Bonn, at the Institute of University of Ro~e, 1940-1947, Professor of Pharmacology Medical School until 1955, Medical School until 1967 and from then to 1984 Director of the Institute of Pharmacology, University of . Ersparmer's work comprised comparative pharmacology and biochemistry of biogenic (17 new compounds) and, particularly, bioactive peptides (40 compounds) from invertebrates and lower vertebrates (amphibian skin) (see p. 184). The opioid peptides (demorphis and deltorphins) are the most potent among all natural peptides.

Fischer. Emil, 1852-1919 (p.24, Plate I), son of a merchant was born in 1852 in Euskirchen (Rhineland) studied chemistry in Bonn (KekuU~), StraBburg (A. Baeyer, physics; A. Kundt) where he graduated Dr. phil. in 1874. Assistant with Baeyer, from 1874 in Munich. Professor in Erlangen (1882- 1885), then in Wiirzburg until his call to the famous Chemical Institute of the University of Berlin as successor to A.W.v. Hofmann, in 1892. and peptide research from 1900, after extremely successful research in the field of carbohydrates and purines. Fisher died in the summer of 1919 in Berlin. He was the second winner of the for Chemistry in 1902, after van t'HotTin 1901.

Fruton. Joseph S. (pp. 56,246, Plate 18), born in 1911 in Czestochowa, Poland Ph.D. at , New York, in 1934, at the Rockefeller Institute with Max Bergmann 1934-1935 (p. 47). In 1945 he became Associate Professor of Physiological Chemistry at Yale University, New Haven, Conn., Chair of the Department of Biochemistry 1951-1967, Eugene Higgins Professor of Biochemistry 1957-1982, Professor of the 1980-1982. Published, among others, General Biochemistry (with S. Simmons, 1953), and Life (1972), and selected articles on the and Chemistry since 1800.

Geiger. Rolf, 1923-1988 (pp.93, 234, Plate 19), born in Bodman on Lake Constance, studied chemistry at the University of Tiibingen (1949) and completed his training in 1956, at the Technical University in Berlin, with a doctoral thesis under Friedrich Weygand. In the following year he initiated peptide chemistry in the Pharma Synthese Laboratories at Hoechst A.G. In 1969, Geiger became the leader of the peptide group. First a part time lecturer at the University of Frankfurt a.M., in 1979 he was named Honorary Professor. With his group he worked successfully on the synthesis of hormones, such as adrenocorticotropin or insulin, and of releasing factors. Among his many excellent coworkers Wolfgang Konig (Plate 20) also a student of F. Weygand, is mentioned here because of his large share in the development of racemization-free coupling methods.

Goodman. Murray (p. 246) born in New York N.Y. in 1928, studied chemistry at Brooklyn College and the Univ. of California and received his Ph.D. in 1952. He was a Research associate at MIT 1952-55, was Prof. of Chemistry at Polytech Institute Brooklyn 1956-71 and is now Prof. of Chemistry, Univ. of California, San Diego. Appendix 267

Gross, Erhard, 1928-1981 (p, 62) was born in 1928 in Wenings near Frankfurt a, M" studied chemi• stry at the Universities of Mainz and Frankfurt. After his Dr. Degree with Th. Wieland he went to Bernhard Witkop at the National Institute of Arthritis and Metabolic Diseases, NIH in Bethesda, Maryland, USA. In 1968 Gross was appointed Chief of the Section on Molecular Structure, Laboratory of Biomedical Sciences, and in 1973 Section Reproduction Research Branch at the National Institute of Child Health and Human Development, NIH. He died tragically in a road accident in 1981. His name is connected with the cyanogen bromide cleavage of pep tides (p. 117), the structure of nisin (p. 222), channel forming peptides, and outstanding literary contributions to the peptide and protein field.

Guillemin, Roger (p. 246) born in Dijon, France, in 1924 studying medicine at the Univ. of Dijon, received his M.D. in 1949 and his Ph.D. at the Univ. of Montreal in 1952. There he became assistant professor and assistant director of the Institute for Experim. Medicine and Surgery (1951-53), then at Baylor College of Medicine, Houston Tex. until 1963. He is now Chairman of the Laboratories of Neuroendocrinology, Salk Institute, La Jolla, Cal. He was awarded the Nobel Prize for Medicine and Physiology (shared with A. Schally) in 1977.

Hirschmann, Ralph Franz (pp. 41,247) born in 1922 in Bavaria, Ph.D. in organic chemistry in 1950 at the University of Wisconsin. Started professional experience in Research Laboratories at Merck Sharp u. Dohme in 1950 and advanced to become director of peptide research, 1968, then of protein research, director medicinal chemistry of the company in West Point, Pa. 1974-76 Vice President of basic research in the Company at Rahway, N.J.

Hodgkin, Crowfoot Dorothy (p. 132, Plate 21) born in 1910 in Cairo, she studied chemistry at Oxford from 1928-32 and concentrated on X-ray with J.D. Bernal at Cambridge; in 1934 she returned to Oxford where she has remained, except for brief intervals, ever since. She became University lecturer and demonstrator in 1946, University Reader in X-ray crystallography in 1956 and Wolfson Research Professor of the Royal Society in 1960-1983. Apart from X-ray studies of insulin (p. 159) she also did research on (in 1942) and on B12 (in 1948). She received the 1964. In 1937 she married Thomas Hodgkin, historian of Africa and the Arab world.

Hofmann, Klaus Heinrich (pp. 38,41,163) born in Karlsruhe, Germany, in 1911, studied chemistry at the Swiss Federal Institute of Technology (ETH, Ziirich), was awarded his Ph.D. in 1936. He became fellow of the 1938-40; assistant at the Medical College, Cornell Univ. 1940- 42; assistant and then associate prof. 1944-47. He has been research prof. of biochemistry and Prof. of the Biochemistry School of Medicine, Univ. of Pittsburgh, Director of Protein Research Laboratories since 1964.

Hofmeister, Franz, 1850-1922 (p. 2, Plate 22) born in Prague, son of a physician, studied medicine at the ancient University, worked on "peptones" (Habilitation). Thereafter, six months with the pharmacologist O. Schmiedeberg in StraBburg (then German Alsace), from 1885-1896 director of the Institute of Pharmacology in Prague. In 1896 professor of Physiological Chemistry, successor of Felix Hoppe-Seyler in StraBburg. After the return of Strasbourg to French rule (1919) he left and found a haven in Wiirzburg, where he was named Honorary Professor and worked on until shortly before his death in 1922.

Hruby, Victor J. (p. 246), born in Valley City, N. Dakota USA in 1938, Ph.D. Cornell Univ. 1965, Prof. of Chern. Univ. of Arizona since 1977. He became interested in peptide hormones as a postdoctoral fellow with Nobel prize-winner at Cornell University in the late 1960s just before he joined the University of Arizona faculty. In the 20 years since, he has become a world leader in this important research field (synthesis, isolation, conformations, dynamics, mechanisms of action, and structure-activity relationships of peptide hormones and neurotransmitters and their analogs). He is the editor of the International Journal of Peptide and Protein Research as successor to Choh Hao Li who died in 1988. 268 Appendix

Jorpes, Erik J., 1894-1973 (pp. 166,241, Plate 23) was born on the Finish island Kokar in the Aland archipelago, when Finnland was part of the Russian Empire. He worked together with V. Mutt with great success on the chemistry and physiology of the gastro-intestinal hormones at the Karolinska Institute in Stockholm, Sweden, where he died in 1973.

Karle, Isabella L. (p. 133) born in Detroit, Mich., in 1921, studied chemistry at the Univ. of Michigan, Ph.D. 1944. Associate at Univ. , instructor there and physicist 1946-59, now Head of X-ray analyt. section of U.S. Naval Res. Lab. Washington D.C. Married to (born in 1918 in New York City, Nobel Prize for Chemistry 1987)

Katchalski, Ephraim (Katzir) (pp. 40, 237, Plate 24) born 1916 in Kiev (Ukraine); Hebrew University Jerusalem, 1951-73; Professor and Head of the Dept. Biophys. Weizmann Institute of Sciences, Rehovot; President of Israel 1973-78; 1978 Professor at Tel-Aviv University. Syntheses and properties of polyamino acids are linked with his name.

Katsoyannis, Panayotis (p. 160, Plate 26) born in in 1924, studied chemistry at the National Univ. with L. Zervas; Ph.D. in 1952. Research associate at the Medical College of Cornell Univ. Ithaka N.Y. (1952-56), associate prof. School of Medicine, Univ. of Pittsburgh (1958-64), at Medical Res. Center Natl. Lab. Brookhaven unti11968 now Professor of Biochem. and Chairman Mount Sinai School of Medicine, New York City. The synthesis of insulin was his field.

Kenner, George Wallace (pp.24, 81, Plate 27). Born 1922. Graduated in Chemistry, University of Manchester, 1939. His early research was with A.R. Todd at Manchester and then at Cambridge, on purine and pyrimidine chemistry and the synthesis of nucleosides. In 1957 appointed Head of the Department of Organic Chemistry, University of Liverpool. Elected Fellow of the Royal Society in 1964. Just before his death in 1978 he was appointed a Royal Society Research Professor, holding his appointment at Liverpool.

Lederer, Edgar, 1908-1988 (pp. 129, 232, Plate 28). Born in 1908 in Vienna, Austria, studied Chemistry at University of Vienna (Dr. phil., 1929); postdoctoral research at Kaiser-Wilhelm-Institut Heidelberg, 1930-1933, with Richard Kuhn, where he revived in 1931, Mikhail Tswett's chroma• tography with carotenoide mixtures. He was from 1933-35 Research fellow at the Inst. de Biologie Physico-Chimique, Paris, director of Dept. of , Vitamin Inst. Leningrad 1936-37. After Army service, he carried out research at Laboratoire de Biochimie, Lyon, from 1940 to 1947, then Maitre des recherches with Inst. de Biologie Physico-chimique until 1960. Director Dept. de Chimie Biologique, Inst. de Chimie des Substances Naturelles CNRS 1960-1978. Died in 1988 in Paris. , immuno adjuvants, were among his studies.

Leuchs, Hermann (1879-1945, p.35, Plate 29) born in 1879 in Nuremberg, studied chemistry in Munich and graduated in 1902, Ph.D. with a thesis guided by E. Fischer in Berlin. He then became associate professor there and, in 1926 Associate Director of the Institute of Chemistry of the University. After his discovery of the "Leuchs' substances" (p. 35) in 1906 and some of their reactions he turned to strychnine chemistry on which he worked until his death in the destroyed Berlin in 1945.

Li, Choh Hao, 1913-1987 (p. 246, Plate 30) was born in Canton, China, in 1913 and had his early schooling there, graduating from Pui Ying High School in Canton in 1929, and receiving his B.Sc. in Chemistry from the University of Nanking in 1933. In 1938 he was granted provisional admission to the University of California, Berkeley, and went on there to his doctorate in physical-organic chemistry. It was in the laboratory of Herbert Evans at Berkeley that Li began to develop the techniques that would eventually lead to the isolation and structure determination of several peptide and protein hormones found in the brain including growth hormone and beta-endorphin. From 1950 he headed the Hormone Research Laboratory as Professor of Biochemistry and of Experimental Endocrinology first at Berkely then at San Francisco. After his retirement in 1983 he continued his research and his numerous editorial activities until his death in 1987. Appendix 269

Lipmann, Fritz, 1899-1988 (p. 208) born in Konigsberg, East Prussia in 1899, he became Dr. med. at the Univ. of Berlin in 1924. Assistant at Kaiser-Wilhelm-Institutes for in Berlin and Medical Research in Heidelberg 1927-31, Carlsberg Institute Copenhagen 1932-39, research associate Medical College of Cornell Univ. 1939-41, Head of Biochem. Res. Lab. and Prof. at Harvard Univ. and Mass. General Hospital 1941-47, then Professor at Rockefeller Univ., New York. Nobel Prizefor Medicine and Physiology 1953. Coenzyme A, peptide .

Martin, Archer John Porter (pp. 52, 54, Plate 31) born in 1910 in London, studied chemistry in Cambridge (Ph.D.) worked there in the physical chemical laboratory on nutritional research, then in the Wool Institute Leeds until 1946. Member of staff of the Medical Research Council, director Natl. Inst. Medical Res., Mill Hill (until 1956), later various professorships, e.g. Ecole polytechnique, Lausanne 1980-1983. Nobel Prize in chemistry 1952, shared with R.L.M. Synge with whom he worked in Leeds on chromatographic methods.

Merrifield, Bruce R. (p. 103, Plate 5) was born in Fort Worth, Texas, in 1921. His parents moved to California when he was two years old and it was in California where he received all his education and also his training in chemistry. After two years in Pasadena Junior College he transferred to the University of California in Los Angeles (UCLA). Following graduation he worked for a year at the P.R. Park Research Foundation but returned to UCLA for graduate training in biochemistry. His studies, guided by Professor M.S. Dunn, were concluded with the Ph.D. degree, that was awarded on June 19, 1949. The next day he married Elizabeth Furlong Oater his coworker) and the day after they moved to New York City to joint Dr. D.W. Woolley at the Rockefeller Institute. Since 1959 he has dedicated his research to the solid phase idea and developed his famous method of . Merrifield advanced in rank at the to Professor and received numerous awards and honorary degrees elsewhere. In 1984 he was named John D. Rockefeller professor and in the same year received the Nobel Prize in Chemistry.

Moore, Stariford, 1913-1982 (p. 50, Plate 4). Born in Chicago, Illinois, in 1913. On graduation from in Nashville, Tennessee, with summa cum laude and as a Founder's Medalist, he entered the University of Wisconsin for graduate studies. There he studied organic chemistry under Homer Adkins and worked on his Ph.D. thesis in biochemistry under the guidance of Karl Paul Link, a friend of Max Bergmann whom he joined at the Rockefellerinstitute in 1939. The work involved the determination of amino acids by precipitation with selective used at two different concentrations ("solubility product method") in collaboration with W.H. Stein. During the war Dr. Moore served from 1942 to 1945 in the Office of Scientific Research in Washington, D.C. On returning to the Rockefeller Institute, after Bergmann's death in 1944, Moore continued the effort in collaboration with William Stein applying chromatography and the important "amino acid analyzer" (p. 51). The new method was applied by Moore, Stein and Hirs, in the same laboratory for the elucidation of the primary structure of ribonuclease A with 124 amino acid residues. , in recognition for these invaluable achievements, shared the Nobel Prize in Chemistry in 1972 with W.H. Stein. He held a chair as a visiting professor at the University of Bruxelles, Belgium, and received an honorary doctorate from the same university and was a chair-professor at Rockefeller University. The names of Stanford Moore and William H. Stein are linked together forever. Yet, fate added still another link to their association, a tragic one. In 1982, threatened by paralysis, similar to that of Stein's, Professor Moore took his own life.

Mutt, Viktor (pp. 167,241, Plate 23) was born in 1923 in Tartu, Estonia, moved to Sweden in 1944 after one year in Finnland, worked with E.J. Jorpes with great success on the chemistry and physiology of gastrointestinal peptides at the Karolinska Institute in Stockholm, Sweden.

Ondetti, Miguel Angel (Plate 32) born in 1930 in Buenos Aires, Argentina, completed his studies in chemistry at the University of Buenos Aires in 1957 with a Doctor of Natural Sciences degree received for his work on chemistry under V. Deulefeu. Soon after, he joined the Squibb Institute for Medical Research and continued his research at the Institute, also after his transfer to the in 1960. There, for several years, he participated in an effort, led by M. Bodanszky, toward the synthesis of peptide hormones, including the first synthesis of secretin and became 270 Appendix coauthor of one of the earliest monographs on peptide synthesis. Subsequently Ondetti initiated and led a major endeavor in the area of anti-hypertensive agents that resulted in the discovery of ACE inhibitors (p. 183), a new class of compounds that has gained considerable importance in the treatment of hypertension and other cardiovascular disorders.

Ovchinnikov. Yuri A., 1934-1988 (p.202, Plate 33) born in Moscow, studied chemistry at the Lomonosov Moscow State University and entered in 1960 the laboratory ofM.M. Shemyakin in the Institute of Chemistry of Natural Products (later "Shemyakin Institute of ") of the USSR Academy of Sciences in Moscow. Research on depsipeptides, in 1964 in Ziirich with V. Prelog of cyclic peptides; back to Moscow-membrane active peptides, proteins. After Shemyakin's death in 1970 he became Academician, Head of the institute, and at the age of 40, Vice President of the Academy. He died in 1988 after a two- years struggle with advancing disease.

Patchornik. Abraham (p. 237, Plate 25) born in 1926 in Nes-Ziona, Israel, studied chemistry at the Hebrew University Jerusalem, where he obtained his Ph.D. with Prof. E. Katchalski. In this time he was research assistant at the Weizmann Institute in Rehovot. There he became Professor at the Department of Biophysics in 1968, and Head Department of Organic Chemistry in 1972. His carrier in Israel was supplemented by a Fellowship with B. Witkop in Bethesda, Md. (1957/58) and Research visits with N.O. Kaplan (Brandeis, 1961) and R.B. Woodward at Harvard, 1965/66. Patchomik developed the field of non-enzymatic degradation of peptides and proteins, e.g. by bromination at the indole and imidazol nucleus, studied photosensitive blocking groups and polymeric reagents.

Pauling. Linus (p. 257, Plate 34) born in 1901, educated at Oregon State College, Calif. Inst. of Techno!. (Caltec) and Universities of Munich, Copenhagen and Ziirich. After being assistant at Oregon State Coli. and Caltec, he was there Asst. Prof. 1927-29, Assoc. Prof. 1929-31, Prof. 1931-64; Prof. of Chemistry Univ. of Calif., San Diego 1967-69, Stanford Univ.1969-74, since then Prof. emer. Member of numerous Academies, among a multitude of degrees and prizes he won the Nobel Prize for Chemistry in 1954, for Peace in 1962. Among numerous fundamental contributions to he suggested secondary structure of peptide chains (with R.B. Corey IX-helix, pleated sheets, p. 13), Vitamin C and longevity.

Photaki. Jphigenia, 1921-1983 (p. 257, Plate 35) born in Corinth, Greece, studied chemistry at the University of Athens. Her research, guided by Leonidas Zervas, led, in 1950, to the degree of Doctor of Natural Sciences. After postdoctoral studies in Switzerland, with Max Brenner and H. Erlenmeyer, and later also with V. du Vigneaud in New York, she rejoined the Department of Chemistry at the University of Athens, advanced in rank and, in 1977, was promoted to full Professor. Her outstanding work, particularly her studies of cysteine- and serine-containing peptides, gained worldwide recognition, but was sadly terminated by her untimely death in 1983.

Rothe. Manfred (pp. 40, 196) born in 1927 in Halle/Saale studied chemistry in Rostock. Habilitation in Halle, transferred to the Univ. of Mainz in 1961 where he became associate Professor in 1966, since 1974 full Professor at Univ. of Ulm (peptides of proline, ).

Rudinger. Joseph. See biography on pp. 155-157.

Rydon. Norman (p. 243, Plate 36) born in 1912 studied chemistry at London (B.Sc. 1931, Ph.D. 1933, D.Sc. 1938), D. Phil., Oxford 1939. Chemical Defence Experimental Section, 1940-1945. From 1945- 1947 Member of Scientific Staff of the Lister Institute, then Reader at Birkbeck College, London, until 1949 and from 1949-1952 Reader at Imperial College, London. Professor at Manchester College of Science and Technology 1952-1957, Professor and Head of Department, Exeter University 1957- 1977. Rydon's work outside of peptide research was on natural substances; peptide topics at Exeter included cysteine peptides, sequential polypeptides, synthetic studies of ferredoxins. Chlorination followed by starchh-potassium iodide for the detection of peptides is known as Rydon-Smith . Appendix 271

Sakakibara, Shumpei (p. 67, Plate 37) born in Kobe, Japan in 1926, graduated from Osaka University in 1951, research associate in the laboratory of Professor Shiro Akabori at Osaka University and received his doctor of science degree from the same University. From 1960 to 1962, he studied in the laboratory of Professor George Hess in Cornell University, Ithaca, where he had an opportunity of handling liquid HF as a solvent of pep tides and proteins. After returning from the Cornell University, he was appointed Head ofthe Peptide Center, Institute for Protein Research, Osaka University as an Associate Professor, he demonstrated usefulness ofHF as a deprotecting reagent. In 1971, he resigned from Osaka University, organized the Peptide Institute in the Protein Research Foundation serving as the research director. In 1977, he organized the Peptide Institute, Inc. outside of the Foundation, served as the president, headed a research group for peptide synthesis and made a success of the Foundation's business of distributing biologically active peptides.

Sanger, Frederick (Plate 38) born in 1918 in Rendcombe (Gloucestershire), studied at St. John's College, Cambridge. Biochemical research at Cambridge from 1940, Ph.D. in 1943, 1951-1983 Member of the Scientific Staff of the Medical Research Council, Nobel prizes in Chemistry 1958 and 1980 for polypeptides (insulin) and nucleic acids, resp. "Sangers reagent", 2,4- dinitrofluorobenzene (p. 115).

Schally, Andrew V. (p. 172) born in Wilno, Poland in 1926, studied biochemistry at McGill Univ. Montreal. Ph.D. 1957. Assistant at Nat!. Institute for Medical Res. (1949-52), associate endocrinologist at Allan Memorial Institute of Psychiatry, Canada (1952-57), assist. prof. protein chemistry and endocrinology at Baylor College of Medicine, Houston, Tex. until 1962, associate prof. unti11966. Prof. School of Medicine, Tulane Univ. New Orleans, Chief Endocrinol. and polypeptide Laboratories at Veterans Administration Hospital. Nobel Prize for Medicine and Physiology 1977 (shared with R. Guillemin).

Schwyzer, Robert (pp. 84,205, Plate 39) was born in Zurich, Switzerland, in 1920, but he received his primary and secondary education in the United States. The family later returned to Switzerland and he studied chemistry in Zurich, completing his experimental work for his Ph.D. degree under . After some years in industry (CIBA), he accepted an invitation to join the faculty of the Federal Institute of Technology (ETH) in Zurich, as professor. Schwyzer first synthesized angiotensin (p. 205), gramicidin S (where he detected cyclodimerization) and, last but not least, the 39-residue sequence of ACTH. He proposed cyanomethyl esters for the formation of the peptide bond. Schwyzer introduced the concepts of "homodetic" and "heterodetic" cyclopeptides. Similar conceptualization of architectural aspects of biologically active peptides and of the relation of sequence and geometry to biological activity was expressed in the nomenclature proposed by him with terms such as "address sequences", "sychnologic organization" (continuate words) and "rhegnylogic organization" (discontinuate words). These thoughts and suggestions, for instance his more recent membrane-compartment model, were not merely intellectually stimulating but also pointed out new directions in hormone research.

Scoffone, Ernesto, 1923-1973 (p. 237, Plate 40) born in 1923 in Udine, Italy, studied at Univ. of Bologna (Ph.D. 1946) and chemistry at Univ. of Padua (Ph.D. 1950). Postdoctoral work at Rockefeller Univ. New York City in 1959/60. From 1960 associate Prof. Univ. Padua, in 1965, full Prof. of organic chemistry at the same Univ., and director of the Centre for Macromol. Chemistry of C.N.R. ScotTone established synthetic peptide chemistry in Italy by work of his group on S-peptide of ribonuclease A, new protecting groups and methods of modification and fragmentation of proteins.

Sheehan, John C. (pp.88, 199, Plate 41) born in Battlecreek, Michigan, 1915, received his Ph.D. degree at the University of Michigan in 1941. After a few years in the pharmaceutical industry (Merck) he joined the faculty of the Massachusetts Institute of Technology where he advanced to full Professor and where he remains actively engaged in research even after his retirement in 1976. He also served as Scientific Liaison Officer of Naval Research and as Editor in Chief of the Journal of Organic 272 Appendix

Chemistry. For his important contribution to the synthesis of , amino acids, peptides, alkaloids and explosives Sheehan has received numerous awards.

Shemyakin, Michail M., 1908-1970 (pp. 20,202, Plate 42). Laid the basis of bioorganic chemistry in the USSR. Academician (1958). Graduated from Moscow State University (1930). Founder and first Director of the Institute for Natural Products, USSR Academy of Sciences. (In 1974 the Institute was given the name "The Shemyakin Institute of Bioorganic Chemistry"). Chemistry of naturally occurring biologically active compounds. With A. Braunstein he developed a general theory of pyridoxal enzyme action. Synthesis of , vitamins, amino acids, quinones, total synthesis (1966). He published many papers on the structure and function of proteins, peptides, and biologically membranes.

Shiba, Tetsuo (p.222, Plate 43) born in Hiroshima Prefecture, Japan in 1924, received his Ph.D. degree at Osaka University in 1959. After having studied at the National Institute of Health, Bethesda, USA, as Visiting Scientist for two and a half years, he returned to Osaka University as Associate Professor in 1962. In 1971 he was appointed Professor, Laboratory of Chemistry, Department of Chemistry, Faculty of Science, Osaka University. Here he developed his structural and synthetic studies on biologically active substances (peptides and others). In the meantime, he served as Vice President of the Chemical Society of Japan, and now as a Member of the Science Council of Japan. He successfully planned the Japan Symposia of Peptide Chemistry and the first international Symposium of Peptide Chemistry in Japan as President of the Organizing Committee in 1987. He retired from Osaka University in 1988, however, he is still continuing his scientific activity as the Director of the Peptide Institute, Protein Research Foundation, Japan, which was founded by S. Akabori.

Stein, William H. 1911-1980 (p. 50, Plate 4) was born in New York City, in 1911. He graduated from Harvard University in 1933 with a B.Sc degree, after one year he transferred to Columbia University. Research guided by Hans Clark, on the protein elastin had a lasting influence on the direction of his scientific interests. Another Columbia professor, Erwin Brand, introduced him to the recently arrived Max Bergmann. Thus, after graduation from Columbia with a Ph.D. degree in 1937 he joined Bergmann at the Rockefeller Institute where he remained throughout his career. At Rockefeller the young researcher was surrounded by other young scientists of real excellence, to name a few: Stanford Moore, Joseph S. Fruton, Emil Smith, Klaus Hofmann, Paul Zamecnik. W.H. Stein participated in an effort aiming at the quantitative determination of the amino acid composition of proteins by the "solubility product" method of Bergmann (p. 48). In the years following Bergmann's death in 1944, Stein and Stanford Moore applied chromatographic procedures for the separation of amino acids in the hydrolysates of proteins, at first partition chromatography, later by application of -exchange chromatography (p. 50). A fully automated instrument, the "amino acid analyzer" was developed in collaboration with D.H. Spackman in 1958. Stein and Moore together with C.H.W. Hirs, addressed themselves to the elucidation of the structure of the enzyme ribonuclease A, and they solved the entire covalent structure of the chain of 124 amino acid residues (p. 51). Dr. Stein's work received wide recognition. When the Rockefeller Institute was reorganized to Rockefeller University he was appointed Professor. In 1972 he received the Nobel Prize in Chemistry (shared with Stanford Moore). In 1980 he died, paralyzed by a rare disease, in New York.

Synge. Richard Laurence Millington (p.52, Plate 44). Born in 1914 in Liverpool, he studied Biochemistry at Cambridge, Int. Wool Seer. 1938, Biochemist at Wool Industries Research Association, Leeds 1941-1943, Staff Biochemist Lister Inst. of Preventive Medicine, London, until 1948, then Head of Dept. of Protein Chemistry, Riwett Research Inst. Bucksburn, Aberdeen (1948- 67), Biochemist, Food Research Institute, Norwich, 1967-1976. Shared Nobel Prize for Chemistry with AJ.P. Martin, 1952 for invention of partition chromatography.

Taschner, Emil, 1900-1982 (p.239, Plate 5) was born in Cracow, studied chemistry there at the Jagiellonian University in 1920, later in Vienna where he received his Ph.D. degree in 1927. After Appendix 273 postgraduate studies in Paris (Pasteur Institute, University) he returned to Cracow to work in the Pharmacological Department and in pharmaceutical industries. The years of World War II he spent in Lwow as a workman in hiding. After the War he moved to the Chemistry Department of the University in Wroclaw, in 1953 he was appointed Head of the Department of General Chemistry at the Technical University of Gdansk, later of Peptide Chemistry Department until his retirement in 1971. Taschner was the founder of peptide chemistry in Poland in the early fifties with studies of protection, deprotection and racemization of amino acids.

Ugi. Ivar (pp. 99,233) born in 1930 in Estonia studied chemistry at the Univ. of Munich, became lecturer there in 1960. Honorary Professor Univ. Cologne in 1967, 1968-1971 Professor of Chemistry Univ. of Southern California, Los Angeles, at present Professor at the Technical University Munich. 4-Component peptide synthesis.

Wang. Yu (pp. 161,231, Plate 46) born 1910 in Hangshou, China, he studied in Nanking, Peking and graduated in 1937 in Chemistry at the University of Munich, Germany. After one-year's postdoctoral work with Richard Kuhn at the Kaiser-Wilhelm-Institute for Medical Research in Heidelberg (1938/39) he advanced via Peking to Shanghai where he, as director of the Institute of Organic Chemistry of the Academia Sinica, has been working in different fields of bioorganic chemistry since 1950. Essentially involved in the synthesis of insulin.

Wessely von Karnegg. Friedrich, 1897-1967 (pp. 29,37, Plate 47). After being severely wounded in the First World War, he studied in Vienna from 1919 and graduated there under Franke in 1922. Among his fellow students, we find names such as Hermann Mark and Richard Kuhn. His interest in amino acids and peptides was aroused during the years 1923-1924 spent in Berlin-Dahlem at the Kaiser Wilhelm Institute for Fiber Research where he worked on silk -fibroin. Although he had other interests, he remained faithful to this area of research for over 30 years. At the 2nd Institute of Chemistry of the University of Vienna he was engaged in studies on carbonyl-bisamino acids and collaborated with E. Spath in work on complex natural products of the terpene series. He was named "Privatdozent" in the early thirties. "Extraordinarius" in 1937 and in 1946 invited to be Professor and Chairman of the Institute for Medicinal Chemistry of the University. After the sudden death of E. Spath in 1948, Wessely was appointed as his successor. His last publication from the peptide field appeared in 1957; he died suddenly in 1967. His life outside the laboratory was dedicated to music, he was himself an accomplished pianist, and to the mountains. An artificial leg notwithstanding he skied in the Alps and was an excellent swimmer. An entry in the books of the Polar Institute of Norway in Oslo shows a Wessely Peak on the Magdalena Fjord in the Spitzbergen.

Weygand. Friedrich, 1911-1969 (pp. 70,129, Plate 48). Born in 1911 in Reichelshausen (Upper Hassia) studied chemistry in Frankfurt a. M., moved in 1934 to the Kaiser-Wilhelm-Institut fUr medizinische Forschung in Heidelberg where he took his doctorate with Professor Richard Kuhn (1935) and worked in the Institute until 1940, interrupted by a one-year's stay at Oxford with Sir Robert Robinson (1935/36). He worked in Heidelberg until 1943 when he moved to the University of Strasbourg, then as associate professor to Tiibingen, in 1955 as Full Professor to the Technical University of Berlin, and finally in 1958 as director of the Organic Chemistry Department of the Institute of Technology (now Technical University) in Munich. Beside peptides (trifluoroacetyl derivatives, gaschromatography, mass , p. 129) his interest was also in carbohydrates and heterocyclic compounds.

Wieland Theodor born in 1913 in Munich, he studied chemistry in Freiburg Brsg. and Munich where he received his Dr. phil. in 1937. From 1937 until 1946 he was assistant, (Lecturer 1941), with Richard Kuhn at the Kaiser-Wilhelm/Max-Planck-Institute in Heidelberg. In 1946 he became Prof. at the Univ. of Mainz. Between 1951 and 1968 he was Prof. and Director of the Institute of Organic Chemistry at the Univ. of Frankfurt. After R. Kuhn's death in 1967, he was appointed Director of the Department of Chemistry, later Natural Products, of the Heidelberg Institute until 1981. He is hon. prof. of the Universities of Frankfurt and Heidelberg. His contributions include electrophoresis on paper of amino acids, peptides and proteins, isoenzymes oflactate dehydrogenase (with G. Pfleiderer), mixed anhydride method of peptide synthesis (p. 79) peptides of (p. 211). 274 Appendix

Witkop, Bernhard (pp. 117,209, Plate 49) was born 1917 in FreiburgjBreisgau. He studied chemistry at University ofM unich and there received his Dr. phil. in 1940 (Heinrich Wieland) and became Lecturer in 1946. He became Mellon Fellow at Harvard University in 1947. Instructor and Lecturer 1948-1950; Special Fellow U.S. Public Health Service 1950-1953. He was at Natl. Institute of Health. Bethesda, Maryland USA. from 1953, there the Chief of the Laboratory of Chemistry of the Institute of Arthritis, Metabolic and Digestive Diseases from 1957 until 1987. Witkop, a very all-round scientist (alkaloids, oxidation mechanisms, pharmacodynamic amines, amphibian venoms etc.), in peptide chemistry, studied hydroxyamino acids, non-enzymatic cleavage of proteins (with E. Gross cyanogen bromide cleavage, p. 117), gramicidins.

Woodward, Robert Burns, 1917-1979 (Plate 50). Born in Boston in 1917, he entered Massachusetts Instutute ofTechnology in 1933 and graduated as Ph.D. in 1937. Postdoctoral fellow at Harvard(1937- 40). Instructor in Chemistry (1941-1944). Assistant Professor (1944-46), Associate Professor (1946- 50), Professor from 1950 until his death in 1979. Nobel Prize in Chemistry 1965, "for his outstanding achievements in the art of organic synthesis". Wood wards reagent (p. 90), synthesis of C (p. 200), polY-IX-amino-acids (p. 37).

Wunsch, Erich (p. 168, Plate 51) born in 1923 in Reichenberg, Bohemia, began studying chemistry in 1941 at the Karls-University, Prague, and after Army service and being a prisoner of war, resumed his studies in Regensburg, Bavaria, in 1946. Graduated Dr. rer. nat. at the Ludwig-Maximilian University in Munich in 1956 and Dr. habil at the Technical University in Munich in 1956. There he was nominated professor in 1973 at the same time he was scientific member of the Max-Planck• Gesellschaft, and director of the department of peptide chemistry at the Max-Planck-Institute for Biochemistry in Martinsried near Munich. Methods of protection in peptide synthesis, synthesis of hormones, author of 2 volumes, Peptides in Houben-Weyl-Miiller's handbook (see p.62) are among his achievements.

Yajima, Haruaki (p. 238, Plate 52) born in Takakarazuka, Japan, in 1925, received his Ph.D. degree as an alkaloid chemist at the Kyoto University in 1956. He then studied peptide synthesis with Klaus Hofmann in the Department of Biochemistry at the University of Pittsburgh until 1962, mainly contributing to the first synthesis of a tricosapeptide with full ACTH activity (p. 164). He returned to Japan in 1962 as Associate Professor at Kyoto University and was promoted to full Professor in 1973. After his retirement in 1989, he moved to Niigata College of Pharmacy as president. Synthesis of a great number of biologically active peptides, also ribonuclease. A are some of his accomplishments.

Young, Geoffrey Tyndale (pp. 95,244, Plate 53). Born 1915. Graduated in Chemistry at the University of Birmingham in 1936. Then moved to Bristol University, working on carbohydrates with E.L. Hirst. In 1938, he received his Ph.D. and was appointed Assistant Lecturer. In 1939-1943, he did war research on explosives at Bristol University. From 1943 to 1945 he was with the British Commonwealth Scientific Office at Washington, U.S.A., exchanging information on war research. In 1947, he was elected Fellow and Tutor in Chemistry, Jesus College, Oxford; 1952, University Lecturer in Organic Chemistry; 1970 Aldrichian Praelector in Chemistry. 1973-1977, Acting Principal, Jesus College, Oxford. 1982, Emeritus Fellow, Jesus College. 1983, O.B.E. (Order of the British Empire). One of the founders of the European Peptide Symposia in 1958.

Zahn, Helmut (p. 161, Plate 54) was born 1916 in Erlangen and studied chemistry and graduated at the Technical University in Karlsruhe (Dr. Ing. in 1940). From 1940 to 1949 he was assistant to Professor El6d at the Institute for Textile Chemistry in Badenweiler, Baden, from 1949-1957 Assistant, Lecturer and Associate Professor at the University of Heidelberg. From 1952-1985 he was Director of the German Institute for Wool Research and in 1960 was appointed full Professor at the Technical University in Aachen. With his team (Plate 54) he was the first to obtain insulin by .

Zervas, Leonidas, 1902-1980 (p. 46, Plate 55) was born in Megapolis in the Peloponese, Greece. He studied chemistry at the University of Athens and then in Berlin where, in 1926, he received his Ph.D. Appendix 275 degree. The experimental work leading to this degree was carried out in Dresden at the Kaiser Wilhelm Institute and was gruided by its director, Max Bergmann (see p. 44). After graduation, Zervas remained in Dresden as research associate; a few years later he was promoted to Head of the Organic Chemistry Section and then to Associate Director of the Institute. After the resignation of Bergmann in 1933, Zervas stayed in Dresden to complete the ongoing studies but a year later he followed Bergmann to New York City to participate in his research at the Rockefeller Institute. In 1937 Zervas returned to Greece where he was appointed Professor at the University of Thessaloniki. Two years later he accepted an invitation to the University of Athens, where he remained, even after his retirement in 1968. He became a member of the Academy of Athens, was named, in 1964, Secretary ofIndustry and was one of the initiators of The National Hellenic Research Foundation. In spite of such new responsibilities he continued to be active in the laboratory until the end of his life. His carbobenzoxy group and the consequences for peptide chemistry are discussed in chapter 3. Author Index

Boldface page nwnbers refer to illustrations

Abderhalden, Emil 3, 31,34, 35, 44, 51, Baumann, E. 5 114-118, 235, 250, 264 Baumert. A 235 Abel, 1.1. 153, 157 Bayer, Ernst 54, 55, 234, 250, 264 Abraham, E.P. 200, 243 Bayliss, W.M. 136 Acher, Roger 232, 245 Beecham, AC. 229 Acs, G. 207 Begg, G. 229 Akabori. Shiro 116, 117,238,250,264 Begg, C. 119 Albaricio, F. 240 Behrens, O.K. 15, 245 Albertson, N.F. 65,83 Belleau,B. 91,230 Amaral, M.J.SA. 240, 244 Ben-Ishai, D. 64, 237 Amiard, G. 232 Benedetti, E. 238 Amiradzibi, S. 14 Benoiton, L. 96, 230, 244 Anantharamaiah, G.M. 236 Berger, A. 39, 64, 237 Anastasi, A 185, 238 Bergmann, Max 3,4, 44ff, 68, 114, 117, Anderson, G.W. 82,95,143,246 118,138,154,195,235,244,264 Anfinsen, C.B. 237,246 Bernardi, L. 238 Antonov, V.K. 247 Berse, C. 230 Aoyagi, H. 239 Berzelius, J. 5, 228 Arens, I.F. 88, 242 Best, Charles H. 153, 157, 230 Arnon, R. 237 Beyennan, H.C. 243 Arns~H.R.V. 199 Biemann, Klaus 128, 264 Arold, H. 235 Birkofer, Leonhard 69 Aston, F.W. 128 Birr, Ch. 67,233 Atherton, E. 244 Bishop, C.J. 222 Audrieth, L.F. 154 BI8ha, Karel 122,231,250,264 Blake, J. 246 Bloch, Ignaz 44, 125 Bloemhoff, W. 243 Baeyer, A 25, 32, 33 Blombll.ck, E. 241 Bajusz, S. 164, 236 Blombll.ck, B. 241 Balaspiri, L. 236 Blout, Elkan R. 39,41, 124, 203, 209, 230, Balbiano, L. 24 245 Ballard, D.G.H. 40 Blumberg, P. 114 Bamford, C.H. 40, 41 Blundell, T.L. 244 . Banting, F.G. 153, 157,230 Bodanszky,~os 85,145,236,246,264 Barany, G. 108, 246 Boissonnas, RA. 81, 85, 145, 185, 245 Barber, M. 130 Boon, P.I 243 Barbieri, J. 6 Borin, G. 237 Barger, George 7, 15, 154, 193 Borsook, H. 57 Barton, MA. 230 Bosisio, B. 238 Bartos, I. 232 Bossert, H. 242 Bauer, W. 242 Botes, D.P. 222 278 Author Index

Boucher, R. 230 Clauson-Kaas, N. 19 Bourgois, A. 6 Clemo, O.R. 155 Bouveault, L. 7 Cole, S.W. 6 Braconnot, H. 5 Colombo, R. 238 Bragg, W.L. 131 Consden, R. 14, 52, 205 Bragg, W.H. 131 Copp, D.H. 170 Brand, E. 205 Corey, Robert B. 41, 132 Brandenburg, D. 234 Coy, D.H. 246 Brazhnikova, M. 203 Craig, Lyman C. 55, 56, 137, 139, 155, Bremer, H. 234, 262 194,203,245,252,265 Brenner, Max 37, 58, 93, 98, 196, 242, Cramer, E. 6 251,265 Cuatrecasas, P. 237 Bricas, E. 232, 235 Curtis, R.W. 20 Brill, R. 3 Curtius, Theodor 24-31, 32ff, 77, 79, 145, Brinkhoff, O. 262 265 Brockmann, Hans 38, 117, 118,201,224, 251,265 Brown, IC. 168 Dale, J. 239 Bruckner, Victor 41,236,251,265 Dale, H.H. 137, 193 Brunfeldt, K. 231 Das,B.C. 129,232 Buckingham, D.A. 239 Day, A.R. 85 Buku, A. 246 de Castiglione, R. 238 Bumpus, P.M. 182, 246 de Meyer, I 157 Bunsen, Robert 33 de Wahl, H.A. 183 Bystrov, V.P. 247 Deber, C. 230 Deisenhofer, Johann 132 Denkewalter, R.O. 41 Calm, R.S. 10 Dessaignes, V.D. 5 Cahours, A. 5 Determann, H. 55, 233 Calderon, I 229 Di Bello, C. 237 Callahan, P.M. 95,246 Diels, Otto 34 Carlsson, L. 241 Dittmer, W. 6 Carpenter, P.H. 245 Dixon,O.H. 160,230 Carpino, L.A. 65, 70, 107,246 Doleschall 89 Carr, F.H. 193 Donohue, J. 132 Carter, H.E. 7 Dormoy, J.R. 232 Cash, W.D. 245 Doty, P. 122 Castro, B. 92 Drabarek, S. 240, 245 Ceprini, M.Q. 85 Drechsel, E. 6 Cham, E. 198 du Vigneaud, V. 15, 44, 45, 64, 71, 137- Chamberlam, IW. 68 152, 153ff, 199, 228-232, 237, 245 Chambers, D.C. 121 Du, Y.C. 230,231 Chandramouli, N. 237 Dubos, R. 203, 207 Chang, W.C. 231 Duisberg, Carl 32, 33 Chantrenne, H. 77 Durieux, C. 232 Chen, P.M.P. 230 Dyckes, D.P. 245 Cheng, L.L. 231 Chi, A.H. 231 Chillemi, F. 238 Eberle, Alex 241 Chimiak, A. 240 Edkins, J.S. 136 Chipens, OJ. 248 Edman, Pehr V. 118, 119, 139, 155, 229, Chorev, M. 237 240, 251, 265 Chu, S.Q. 231 Ehrlich, Pelix 7 Chung, D. 246 Ellinger, A. 6 Claisen, L. 90 Elliot, D.P. 244 Author Index 279

Emery, AR. 82 Gaddum, J.H. 184 Erickson, B.W. 245 Galpin, 11. 244 Erlanger, B.F. 205 Gause, Georgyi 203 Erlenmeyer, E. 5, 6 Gebert, U. 221 Ersparner, Vittorio 166, 184, 185, 238, Geiger, Rolf 87,93, 110,233,234,253, 252,266 266 Euler, K.E. 37 Gelling 157 Gerlach, H. 203 Gevers, W. 208 Gibbons, W. 244 Fairlarnb, AH. 18 Gierasch, L. 246 Faraday, M. 1 Gil-Av, E. 55 Farrington. J.A. 85, 244 Gillessen, D. 245 Farthing 36,40 Gilon, C. 237 Fasman, G.T. 122 Giralt,E.240 Faulstich, H. 217,233 Glass, 1. 245, 246 Ferger, M. 245 Goffinet, B. 232 Fennandjian, S. 232 Gold, V. 82 Finn, F. 246 Goldblatt, H. 181 Fischer, Emil 2, 4, 6, 10, 13, 27-31, 32ff, Goodman, Murray 246, 266 44,46,53,54,67,69,77,235,266 GlSrdeler, J. 68 Fischer, H.O.L. 33 Gordon, AH. 205 Fischer, Laurenz 33 Gordon, M. 14,52, 85 Fischer,Otto 33 Gorup-Besanez. E.v. 6 Fin, P.S. 245 Goutarel 224 Fiwne, Luigi 220 Grassmann, Wolfgang 56, 233 Flarnand, C. 6 Gray, W. 116 Fleming, Alexander 198 Greenstein, J.P. 7 Fletcher, G.A. 244 Gregory, RA. 136 Flodin, Per 55,241 Grimaux, E. 2, 24 Florey, H.H. 198 Gross, Erhard 62, 117, 222, 246, 267 Flouret, G. 245 Gross, R.E. 48 Folch, Georg 240 Griltzmacher, H.F. 129 Fontana, A. 237 Grzonka, Z. 240 Ford, W.W. 211 Guillemin, Roger 172, 246, 267 Foster, G.L. 114 Gulevitch, W. 14 Fourneau, E. 2 Gurd, F.RN. 245 Fox, Sidney 38 Gut, V. 231 Fraenkel-Conrat, Heinz 47, 57, 60 Gutte, B. 245 Frank, V.S. 78 Guttmann, S. 242 Frankel, M. 38, 237 Freudenberg, Karl 46 Fric,l. 231 Habermann, E. 186 Fridkin, M. 237 Hagenmayer, H. 234 Friedmann, E. 5 Hallermayer, R. 211 Friedrich, Walther 131 Han, G.Y. 70, 107 Fromageot, P. 232 Hansen, Bruno 231 Fromageot, C. 117, 232 Harding, V.J. 52 Fruton, Joseph S. 3, 47, 56, 61, 246, 252, Hardy, G.W. 244 266 Hardy, P.M. 243 Fuchs, H. 36, 40, 49 Harington, Charles R. 15,65, 141, 154 Fujii, Nobutaka 170, 239 Hartmann, F. 79 Fujino, Masahiko 239 Hassal, C. 244 Fukuda,K. 161 Hauptmann, J.A. 133 Funk, K.W. 247 Havinga. E. 243 280 Author Index

Heartley, B.S. 116 Jensen, Hans 153 Hedin, S.O. 6 Jentsch. J. 186 Helferich. Burckhardt 13,67,68 Jeschkeit, H. 235 Hermann, Peter 235 Jiang, R.Q. 230 Hess, O.P. 88 Joaquina, M. 240 Heymens-Visser, O. 243 Johansen, J.T. 60,231 Heymes, R. 232 Jlihl, A. 245 Heyns, K. 129 Jones, D.S. 244 Hirs, C.H.W. 51 Jorpes, IE. 136, 166, 167, 169, 241, 254, Hirschmann, Ralph F. 41, 247, 267 268 Hiskey, R.O. 73, 246 Jost, K. 146,231 Hlavacek, J. 231 Jung, O. 234 Hoagland, M. 207 Hodges, R.S. 230 Hodgkin, Dorothy C. 159, 244, 253, 267 Kader, A.T. 70 Hofmann, Klaus H. 38, 41, 163, 245, 267 Kaiser, E.T. 245 Hofmann, A. 194 Kajtar, M. 236 Hofmeister, Franz 2, 253, 267 Kamber, B. 73, 242 Holley, Robert W. 155, 245 Kamm, O. 137 Holst 68 Kann, E. 117 Holzwart, O. 122 Kapfhammer, J. 48 Honzl,1. 41, 231 Kappeler, H. 242 Hoogerhout, P. 243 Karle, Isabella L. 133, 215, 246, 268 Hope. D.B. 244, 245 Karle, Jerome 133 Hopkins, F.O. 6,15 Katchalski, Ephraim 38, 39, 40, 237, 254, Homer, Leopold 26 268 Hlirnle, S. 234 Katsoyannis, P.O. 73, 152, 160, 161, 235, Houghten, RA 111,246 245,246,255,268 Hruby, Victor J. 245, 246, 267 Katzir see KatchaIski, E. Hsing, C.Y. 231 Kaufmann, H.P. 216 Hsu, J2. 231 Ke, L.T. 231 Hu, S.C. 231 Kekule, A.v. 1 Huang, W.T. 231 Kemp, D.S. 97,245 Huber, Robert 132 Kendrew, J.L. 5, 132 Huffmann, O.W. 247 Kenner, O.W. 81, 85, 95, 230, 244, 255, Hughes, I 187 268 Huguenin, R. 242 Kent, S.B.H. 245 Hunkapiller, M.W. 120 Kerling, K.E.T. 243 Kessler, H. 127, 216, 234 Khan, SA 236 Ingold, C.K. 10 Khorana, H.O. 88 Iselin, B. 242 Khosla, M.C. 182, 246 ltoh. Masumi 239 Kidd, D.AA 69 Ivanov, V.T. 215, 247, 248 King, F.E. 69 Ivanovics, O. 41, 236 Kiryushkin, A.K. 247 Izdebski, J. 240 Kisfaludi, L. 85, 236 lzumiya, Nobuo 207,239 Klausner, Y.S. 237 Kleinkauf, H. 208 Klostermeyer, H. 234 Jacobs, JJ\. 55, 194 Knippling, Paul 131 Jaeger, E. 233 Knorr, Ludwig 33 Jakubke, H.D. 61, 235 Knowles, R.I 244 James, A.T. 54 Koenigs, W. 32 Jaquenoud, PA 242 Kofod, H. 231Kolbe, H. 25 Jarvis, D. 243, 245 Klinig, WA 234 Author Index 281

Kemdg, VV. 55,87,93,110,233,234,253 Maassen van den Brink, VV. 243 Kopple, K.D. 246 MacLean, R.M. 52 Kornet, M.J. 103, 104 Magee, M.z. 38 Kossel, A. 6, 48 Magendie, F. 1 Kostansek, E.C. 221 Malek, G. 91 Kosterlitz, H.VV. 187 Mancheva, I. 229 Kovacs, J. 85, 96 Manning, M. 151, 245 Kovacs, K. 236 Marchiori, F. 237 Kraut, K. 79 Marcussen, Jan 231 Kuhn, Richard 48, 49 Marglin, A. 161, 245 Kung, Y.T. 231 Markovnikov, VV. 6 Kunitz, M. 56 Marquarding, D. 233 Kunz, H. 233 Marquet, A. 232 Kupryszewski, G. 240 Marsch, R.E. 132 Kurahashi 208 Marshall, G.R. 108, 245, 246 Martin, A.lP. 14, 52, 54, 114, 205, 243, 256,269 Martinez, Jean 232 Laland, S.G. 208 Marvel, C.S. 153 Laschi, R. 220 Matsueda, R. 239 Laskowski, M. 58 Mazur, R.H. 247 Latham, P.VV. 1 McKay, F.C. 65 Laursen, RA. 120 Mead, T.H. 15, 65 Lebl, M. 231 Medzihradszky, K. 236 Lederer, Edgar 48, 129, 232, 255, 268 Medzihradszky-Schweiger, H. 236 Lehn, J.M. 203 Meienhofer, J. 62, 81, 233, 245, 262 Meister, A. 18, 245 Lempert 89 Lentz, K.E. 182, 246 Merrifield, R.B. 67, 104-112, 161, 213, 245,247,269 Leplawi, M.T. 240 Meyer, C.E. 7 Letsinger, R.L. 103, 104 Meyer, Victor 33 Leuchs, Friedrich 35 Michel, Hartmut 132 Leuchs, Hermann 6, 35f, 255, 268 Michl, H. 229 Leuchs, Georg 35 Miekeley, A. 117 Lewis, H.B. 153 Miller, J.G. 85 Li, Choh Hao 231,246,256,268 Minkowski, O. 157 Liberek, B. 240 Mitchell, A.R. 245 Liebig, J.v. 5 Mitin, Y. 247 Light, A. 245 Miyazawa, T. 123,124 Likiernik, A. 5 Mladenova-Orlinova, L. 229 Lilienfeld, L. 24 Montecucchi, P. 238 Limpricht, H. 5 Moore, Stanford 48, 50, 51, 61, 138, 155, Lindeberg, G. 241 245,269 Lipmann, Fritz 155,207,208,245,268 Moore, C. 201 Lipp, A. 5,6 Morley, 1 244 Loew, Oscar 1 M6rner, KA.H. 5 Loffet, A. 229 Moroder, L. 233, 237 Loh, T.P. 231 Mueller, lH. 7 Loquin, R. 7 Mukaiyama, Teruaki 98, 239, 247 Losse, G. 234 Mulders, G. 1 Low, M. 236 Munekata, E. 218,233,239 LUbke, K. 234 Munk, E.M. 90 Lucente, G. 196,238 Muramatsu, Ichiro 238 Lundell, E.O. 245 Murlin, J.R. 44, 153 Lynen, Feodor 78, 208, 211 Murti, V.V.S. 237, 245 282 Author Index

Musso, H. 38 Piria, R. 6, 15 Mutt., Viktor 136, 166-169,241, 254, 269 Pitt-Rivers, R.V. 141 Mutter, M. 234, 242 Piutti, A. 6 Muzalewski, F. 240 Plattner, PA. 19,20 Pless, J. 85, 242 Poduska, K. 231 Nager, U. 20 Popenoe, E.A. 245 Natarajan, S. 237 Porath, Jerker 55,241 Nefkens, G.H.L. 70, 85, 243 Pravda, M. 231 Nestor, JJ. 245 Pre1og, V. 10,203 Nesvadba, H. 229 Pressman, B.C. 201 Neumeister, R. 2,6 Prox, A. 129, 233 Newton, G.G.F. 200, 243 Purcell 125 Nicolaides, E.D. 183 Pyman, F.L. 6 Niedricb, N. 234 Niemann, C. 3 Niu, C.I. 231 Nivard, R.IF. 243 Rachele, J.R. 245 Noble, R.L. 246 Ragnarsson, U. 241 Northrop, IH. 56 Ramachandran, GN. 236 Nutt., R.F. 247 Ramachandran, J. 246 Ramage, R. 244 Reichert., E. 78 Obermeier, R. 234 Ressler, C. 139, 245 Offord, R.E. 242, 244 Richardson, W.L. 206 Okawa, K. 238 Ridge, B. 243 Okuda, T. 234 Riniker, B. 73, 242 Ondetti, Miguel A. 183, 246, 256, 269 Rittel, W. 242 Osato, R.L. 82, 141 Rittenberg, D. 114 Ovchinnikov, Y A. 202, 215, 247, 248, Ritthausen, H. 6 256,270 Rivier, J. 246 Robinson, Robert 154 Robiquet., P. 5 Pacsu, E. 38 Rocchi, R. 237 Page,I.H. 182,246 Roeske, R.W. 245 Panneman, H.J. 242 Romeo, A. 196 Paolillo, L. 238 Roques, B.P. 232 Pasteur, Louis 198 Rose, W.C. 7, 153 Patchomik, Abraham 68,237,254,270 Roser, K.L. 196 Patel, 0.1 215 Rothe, Manfred 40,196,207,234,270 Pauling, L. 41, 132, 257, 270 Rudinger, Josef 41, 145, 146, 147, 152, Pedersen. CJ. 203 155ff,231 Pedone, C. 238 Ruhemann, S. 51, 113 Pedroso, E. 240 Ry~H.Norman 38,243,258,270 Peggion, E. 237 Rzezsotarska, R. 240 Penke, B. 236 Perseo, G. 238 PerulZ, M.F. 5, 132 Sachs, H. 205 Photaki,Iphigenia 37,73,235,242,245, Said, Sl. 168 257,270 Sakakibara, Shumpei 67, 107, 145, 167, Piche, L. 230 169, 238, 258, 270 Pierce, IG. 245 Sakarellos, A. 235 Pietta, G. 108,238 Sakarellos, C. 235 Pine, N.W. 15 Sakarellos-Daitsiotis, M. 235 Pinnen. F. 238 S~ E. 185, 242 Author Index 283

Sanger, Frederick 2, 115, 116, 138, 155, Sorm, F. 155 158,159,228,258,271 Spackman, D.H. 51 Sarges, R. 209 Spangenberg, R. 72 Sato, M. 238 Sparrow, J.T. 246 Sawyalow, W.W. 57 Spatola, AF. 246 Scatturin, A. 237 Spies, I.R. 121 Schaal, E. 24 Staab, HA 91 Schally, AJKkew V. 172,271 Stahl, E. 53 Schattenkerk, C. 243 Stammer, I. 246 Schiff, H. 24 Starling, E.H. 136 Schiller, P.W. 164, 230, 241 Staudinger, H. 4 Schinner, R.H. 5 Stedman, J. 245 Sch16gl, K. 229 Steglich, W. 98, 233 Sclunidt, Ulrich 225, 234 Steiger, E. 6 Sclunidt-Kastner, G. 201 Stein, William H. 4,48,50, 51, 61, 138, Sclmabel, E. 65, 234, 262 155, 244, 272 Schlin, I. 236 Stelakatos, G.C. 235 Schlinheimer, Rudolf 46, 64 Stevens, C.L. 90 Schramm, C.H. 37 Steward, J.M. 245 Schramm, G. 38 Stewart, F.H.C. 229, 245, 246 Schr6der, E. 234 Stirling, C.J. 70 Schulz, G.E. 5 Stirpe, F. 220 Schulze, E. 5,6 Stix, W. 115 SchUtzenberger, P. 2, 6, 24 Stoev, S.B. 229 Schwab, G.M. 49 Stoll, Arthur 193 Schwarz, H. 182 Stouffer, J.E. 245 Schwyzer, Robert 65, 68, 84, 164, 205, Strecker, A 6 207,230,241,258,271 Studer, R.O. 207, 242, 245 Scoffone, Ernesto 237,259,271 Svedberg, T. 4 Scott, D.A. 230 Swan, J.M. 228, 245 Sealock, R.R. 146 Synge R.L.M. 52, 114, 205, 243, 260, 272 Sela, M. 40, 237 Szelke, M. 236, 244 Sheehan Jolm.C. 69, 78, 88, 90, 108, 199, 200,206,245,247,259,271 Shemyakin, M.M. 20,202, 247, 248, 259, Tam, I.P. 245 272 Tamburro, AM. 237 Sheppard, R.C. 244 Tamussi, P A. 238 Sheraga, H. 246 Tang, K.L. 231 Shi, P.T. 231 Tanret, Ch. 193 Shiba, Tetsuo 224, 238, 259, 272 Tasclmer, Emil 239, 260, 272 Shimonishi, Y. 107, 145, 238 Tatemoto, H. 241 Sieber, P. 68, 73, 164, 205, 207, 242 Tesser, G.1. 85, 243 Siemion, IZ. 240 Theodoropoulos, D. 71,235 Sigmund, F. 37 Thomas, D.W. 232 Shnrnonds, S. 245 Thompson, E.O.P. 228 Sivanandaiah, K.M. 236 Thunun, G. 38 Sj~berg, B. 241 Tiselius, Arne 4, 49 Skeggs Jr., L.T. 182,246 Titlestad, K. 239 Skroka, W. 234 Tobschirbel, A 216 Sluyterman, LAE. 38 Tolle, I.C. 247 Smeby, R.R. 182, 246 Tomatis, R. 237 Smith, Emil L. 56 Tometsko, A 161 Smith, P.W.G. 38 T6morkeny, E. 236 Snell, E.E. 114 Tonelli, A.E. 215 S6rensen, S.P.L. 4, 6 Toniolo, C. 237 284 Author Index

Tracy, HJ. 136 Weigert, F. 6 Trasciatti, D. 24 Weisz, E. 236 Tregear, G.W. 111 Wenger, R.M. 211 Trippet, S. 139 Wessely von Karnegg, F. 29, 37, 39, 40, Troensegaard, N. 3 41, 229, 260, 273 Trudelle, Y. 232 West, H.D. 7 Tsou, L.C. 230 Weygand, Friedrich 54, 64, 97, 129, 233, Tswett, M.S. 49 234,261,273 Tuppy, H. 140,229 Wieland, Heinrich 211, 212 Turba, Fritz 49 Wieland, Theodor 7,37,53,55,78,79,80, Turner,1.M. 85 84, 233, 239, 273 Tzougraki, C. 235 Wieland, Ulrich 211 Wilchek, M. 237 Williams, N.W. 244 Udenfriend, S. 52,62 WillsWter, Richard 6, 56 Ueki, M. 239 Wilson, E.I 38 Ugi, Ivar 99, 233, 273 Winitz, M. 7 Urry, D.W. 209 Wintemitz, F. 232 Winterstein, E. 6 Wintersteiner, Oskar 153 Vajda, T. 236 Wissmann, H. 234 van Binst, G. 229 Witkop, Bernhard 117,209,212, 246, 261, van Nispen, I.W. 243 273 van Rietschoten, P. 240 Wolff, L. 6 van Rietschotten, I. 232 Wollaston, W.H. 5 van Slyke, D.D. 114 Wohnan, Y. 237 Vaughan Ir., I.R. 81, 82, 141, 246 Woodruff, H.B. 224 Vauquelin, L.N. 5 Woodward, Robert B. 37, 90, 200, 245, Vavrek, R.I 245 261,274 Veber, D.F. 72, 247 Wooley, D.W. 245 Velluz, L. 71 Wrinch, Dorothy 3 Verdini, S. 238 wUnsch, Erich 56, 62, 71, 72, 168, 233, Verhart, C.G.I. 243 261,274 Vidali, G. 237 Wilthrich, K. 242 Virtanen, A.I. 59 Wyckhoff, R.W.G. 132 Vlasov, G.P. 247 Vogler, K. 242 von Bunge, Gustav 34 Yajima, Haruaki 170,238,262,274 von Euler, U.S. 184 Yamashiro, D. 245, 246 von Hofmann, August Wilhehn 33 Yanaihara, C. 238 von Laue, Max 131 Yanaihara, N. 238 von Mering, I. 157 Yich, Y.H. 231 Yiotakis, A.E. 235 Wade, R. 244 Young, Geoffrey T. 95,262,274 Waksman, S.A. 224 Waldsclunidt-Leitz, Ernst 49, 56 Waley, S.G. 18,41 Zabel, R. 234, 262 Walter, R.W. 245 Zachau, H.G. 207 Wang, S.S. 108 ~Hehnut 72,73,161,229,262,274 Wang Yu 73,231,260 273 Zanotti, G. 197, 238 Warburg, Otto 29 Zaoral, M. 231 Wardlaw, A.C. 160, 230 Zemplen. G. 235 Wasteneys, H. 57 Zervas, Leonidas 44, 46, 47, 61, 65, 71, Weber, U. 234 73,154,235,257,263,274 Weigele, M. 52 Zuber, H. 242 Subject Index

Page numbers in italics refer to figures and formulas

ACE (angiotensin converting enzyme) 181- Acyloxyphosphonium salts 92 183, 186 Acyloxyphosphonium compounds 247 - inhibitors 246, 270 N-Acylserine 85 Acetamido-methyl group 72 N-Acylseryl-glycine amide 197 Acetate, active 78 N-Acylthreonine 85 Acetic anhydride 79 Acyltripeptide methylester, MS 129 Acetic acid 110 N-Acylureas 93 - -, activated 208 -, derivative 90 Aceturic acid 25, 79 Adenosine triphosphate (ATP) 77,208 Aceturyl peptides 26 S-Adenosyl- 211 Acetyl chloride 29, 79, 80 Adrenal gland 163 S-Acetyl coenzyme A 78 Adrenocorticotropin (ACTH) 163, 188, N-Acetylglycine 25, 46 236, 241, 266, 274 - ethyl ester 46 Affinity binding, enzymes 57 N-Acetylglycyl-N-acetylglycine ethyl ester Affinity labeling, hormone receptors 241 46 Alamethicin 210f N-Acetylleucyl-proline 128 6 N-Acetylpeptides 129 -, NMR 125 - esters 129 -, ~-oxindol- 217 Acetylphenylalanylalanylglycine amide 56 -, X-ray crystallography 132 Acetyl phosphate 77, 78 Albumin 1 Acid alumina column 50 Alburninoids 1 Acid azides 77 Albumoses 2 Acid-labile protecting groups 67 Alkaloids, ergot 3, 193f, 265 Acidolysis 66, 68, 105, 233 -, neurotoxic 222 ACfH 163, 188, 236, 241, 266, 274 -, peptides 224, 234 -, human, amino acid sequence 163 -, strychnine 36 -, stepwise chain-lengthening with active Alkyl carbonic acid mixed anhydrides 81 esters 164 Alkylchlorocarbonate (chloroformate) 80 Actin filaments, stabilization, Alkylesters, saponification 69 218 Allyloxycarbonyl group 67 Actinomyces 203 Alytesin 186 Actinomycins 120,224,224,265 219 Actin, phallotoxinslvirotoxins 218 220 O-Acyl-N-dialkyl-hydroxylamines 86 Amanita research 233,273 Acyl amino acid thiophenyl esters 84 217 -- -/trimethylacetic acid 83 211, 212, 216, 217, O-Acylaminoacyl-piperidines 86 219 Acylimidazoles 91 Amanita tenuifolia 217 O-Acylisourea derivatives 89-94 217 Acyl migration 90 Amanitatoxin 211 N-Acylnitroarginine 85 Amanitin 212,217-221 286 Subject Index

Amanullin, FAB mass spectrum 131,131 Anhydrides 79ff 217, 219f Anhydrides, mixed 69, 78-87, 142,233, Amberlites 50 242 Amines, tertiary 81 -, -, acyl amino acidsltrimethylacetic acid Amino acid esters, peptide bond fonnation 83 58 -, -, acyl amino acids/ 81 Amino acid chloride hydrochlorides 37 -, -, alkylcarbonic acid 81 Amino-protecting group, easily removable -, -, disproportionation 83 29 -, -, ethylcarbonic acid 91 Amino acids, analyzer 51,269,272 -, -, intermediates 79 -, bifunctional 31 -, -, isobutylcarbonic acid 81 -, C-tenninal 116 -, -, isovaleric acid/acylamino acid 82 -, chromatography 49f,233 -, -, phosphoric acid 92 -, chronology 5 -, -, procedure/method 213, 219, 273 -, derivatization 113 -, -, sulfuric acid 244 -, dennorphin 186 Anhydrides, symmetrical 79, 83, 84, 89, -, a-disubstituted 240 94,108,111 -, functional side chains 11 Anhydrocyclols 196 -, hindered 81 Aniline 37, 57, 61 -, one-letter abbreviations 7, 7 2-Anilinothiazolin-5-one 119, 119 -, posttranslational modification 9 (anti-amanitatoxin) 122, 129, -, purification 113 212f,212 -, separation of enantiomeric 234 -, alkali-metal complex 216 -, synthesis 272 -, analogs 214 ' -, thioether 222,223 -, CD spectra 214, 215, 122 -, three-letter abbreviations 7 -, Li+ complex 215 S-Aminoacyl CoA 78 -, synthesis 213 Aminoacyl copolymer 111 -, X-ray diffraction analysis 133, 214, 215 S-Aminoacyl cysteamines 78 Antiarrhythmic action, oxytocin 149 - cysteines 78 Aminoacyl insertion 196,197 Antibiosis 198 L-n-Aminoisobutyric acid 210 activity, ion transport, valino- Aminolysis, cyanomethyl esters 84 mycin 202 -, methyl esters 84 Antibiotics, from Bacillus brevis 204 - reaction, 87 -, penicillins 154 -, thiophenyl esters 85 -, peptides 198f, 242 6-Aminopenicillanic acid 198, 200 -, synthesis 272 Aminopeptidases 150 Antimicrobial spectra 154 Aminothioic acids 37,78 Arginine 6, 48, 49, 62, 107 Ammonolysis 105, 108 Argon gas 130 -, methyl esters 84 Arrhythmia, digitalis-induced 149 -, phenyl/vinyl esters 85 S-Arylcysteine 17 Amphibians, skin peptides 166, 185f Arylesters 85 Ampicillin 198 S-Arylglutathione 17 Anchoring 104, 108 Asparagine 5, 62, 66, 67, 109, 142 - ester bond, cleavage 105 Aspartame 165,244 Angiotensin 77, 1m, 18lf, 188, 243, 244 Aspartic acid 2, 6, 48, 114 -, analogs 182, 243 Aspergillus niger 20 -, antagonists 182 ATP 77,208 -, converting enzyme (ACE) 181, 186 -, X-ray crystallography 132 -, - -, inhibitors 183, 246 Atrial peptides 189 -, release 183 Azacyclols 196,196 Angiotensinogen 182 Azide procedure 145 Angiotensin-renin system 244 Azlactones 44,45,96, 154 Subject Index 287

Bacillus anthracis 41 - -, Boc 68, 105, 107 Bacillus brevis 203 - -, tert-butyl based 107 Barium hydroxide 48 - -, ~-halogenethyl 240 Bates'reagent 92 - -, photo-sensitive 270 Benzotriazolyl-N-oxytridimethylaminophos- - -, selectively removable 239 phoniumhexafluoro phosphate 92 Boc group (tert-butyloxycarbony 1), blocking Benzoylarginine ethyl ester 60 65, 68, 97, 105, 107, 169 Benzoylaspartyltyrosine amide 56 Boc-fluoride 65 Benzoyl chloride 80 186 Benzoyldileucine anilide 57 BOP (benzotriazolyl N-oxytridimethyl• I-Benzoylglucose 46 aminophosphonium hexafluorophos• Benzoylglycine peptides 26 phate), coupling reagent 92, 232 Benzoylglycine anilide 57 Bothrops jararaca 186 Benzoylglycine 57 183f, 185, 186, 235, 244 Benzoylglycylglycine 24, 32, 79 - antagonists 184 Benzoylhexaglycine 27 -, 6-g1ycine- 184 Benzoylleucine 57 Bromelain 60 Benzoyllysine amide 56 Bromine water 138, 144 Benzoylpentaglycine ester 26 Bromoisocaproyl chloride 31 N-Benzoyl peptides 25 Bromoisocaproyltriglycine chloride 31 Benzoyl-polyglycines 32 a-Bromopropionic acid 29 Benzyl alcohol 96 Bunte salts 72 Benzylation, thiol groups 141 Bursin 189 Benzyl bromide 64 sec-Butyl chlorocarbonate 81 Benzyl chlorocarbonate 62 tert-Butyl esters, preparation 240 S-Benzylcysteine 96, 97 tert-Butyloxycarbonyl group see Boc Benzyl esters 66, 142, 202 group - linkage 107 S-tert-Butylthiocysteine 72 Benzyl ethers 66 tert-Butyltrifluoroacetate 95 Benzyl groups 46, 71 S-Benzyl group 107 Benzyl mercaptane 96 Caerulein 166, 188, 238 Benzyloxycarbonyl (carbobenzoxy) group 169, 170f, 246 47,63,97,164,264 - synthesis, formation 170 - -, reduction, sodium in liquid ammonia Calcium hydroxide 48 142 Captopril 183 - derivatives 104 Carba analog, oxytocin 147 Benzyloxycarbonyl-L-proline 142 Carbamoic acid 64 Benzyloxycarbonyl-L-Ieucylglycine ethyl Carbanion 95 ester 141 -, resonance-stabilized 96 N-Benzyloxycarbonyl-S-benzyl-L-cysteinyl- N-Carbethoxy peptides 29 L-tyrosine 141 N -Carbethoxyphthalimide 243 Benzylpenicillin 154 Carbobenzoxy group 44f, 60, 72 O-Benzylserine 96 Carbodiimides 83,84,87,88,90,94, 109, Benzyltrifluoroacetate 64 200, 206, 238 Biogenetic engineering, insulin 163 -, polymeric 237 Biphenylisopropyloxycarbonyl group 107 -. water-soluble 169 Biphenylylpropyl-2-oxycarbonyl (Bpoc) 66 a-Carboethoxy-a-benzyloxypropionyl N-Bisaminoacylamides 196 residue 194 Biuret base/reaction 2, 30 N-Carboethoxyamino acid chlorides 35 Blocked nonapeptides 143 N-Carbonic acid 63 Blocking groups 235, 275 Carbonium ion 66 - -, acid-sensitive 242 Carbonyl-bisamino acids 273 - -, acidolytic cleavage 237 Carbonyldiimidazole (CDI) 91 288 Subject Index

Carboxamide,from benzhydryl resin 109 -, paper 14, 52, 113, 114, 116, 205 Carboxamide group, dehydration 93 -, partition 52, 113, 272 N-Carboxyamino acids 36 -, thin layer 53 N-Carboxyanhydrides 35,229 -, vapor phase 233 'Y-Carboxyglutamic acid 9 Chromogenic substrates 235 Carboxyl group, activation 89,95 Chymotrypsin 57, 117, 157 Carboxylic acid hydrazides 26 Cinnamaldehyde 219 Carboxypeptidases 60, 161, 162, 184, 231 Claviceps purpurea 193 14,64 Co-ill complexes 239 -, synthesis 63,64 CoenzymeA 269 Carotinoids 49 Complexones 21, 203 Casein 1,28 -, macrocyclic 214 Catalysis, bifunctional 243 Condensation, four-center (4CC) 99,233 Cathepsin 60 -, oxidation/reduction 98 CD (circular dichroism) 120, 121 D-Configuration 186 CDI (carbonyldiirnidazole) 94 Conformation, peptide 245 Cephalosporanic acid 199 Copolymers, styrene/divinylbenzene 104 - -, 7-amino- 199, 200 Corticotropin 103, 163ff, 230, 236, 241, 198f, 243 266 -, synthesis 274 Cotton effect 121, 122 -, thiazine ring 200, 201 Countercurrent distribution 55, 137, 143, Cephalosporium acremonium 199,200 265 Cerebellin 189 - -, /oxytocin 155 Cerebellum-specific peptide 188 - -, gramicidins 203 Cerebrogastrointestinal honnonal peptides Coupling, active esters 87 189 -, BOP 92, 232 Chain lengthening, stepwise 145 -, racemization-free 266 Chain tennination 110 - reagents 77,93, 108 Channel-fonning peptides 267 - -, ethoxyacetylene 88, 241 Chemical shifts 125 -, segments 242 Chimeric protein 162 -, side reactions 94ff Chiral compounds 121 Cryptands 203 Chiral phase 55 Crystal structure analysis 132 Chiral purity 93,96,99, 169,230 p-Cyanoalanine 96, 109 Chiroptical methods 122 Cyanobacterium 222 5-Chloro-8-hydroxyquinoline 86 'Y-Cyanobutyrine 109 Chloroacetonitrile 84 Cyanogen bromide 117, 162 2-Chlorobenzyl esters 107 -, peptide cleavage 266, 274 2-Chlorobenzyloxycarbonyl group 107,169 Cyanoginosin-LA 222 Chlorophylls 49 Cyanomethyl esters 84, 271 (CCK) 165f, 168, 188, Cyclic peptides see Cyclopeptides 238 Cyclization 207 -, intestinal extracts 166 -, acid chloride activation 203 -, sulfate ester in tyrosine 166, 167 -, linear peptides 205,206 Cholecystokinin-pancreozymin (CCK-PZ) -, via disulfide fonnation 243 136, 166, 241 Cyclodepsipeptides 195 Chromatography 48f, 114, 119,269 -, enniatins 20 -, affinity 110, 237 Cyclodimerization, gramicidin 271 -, gas 113, 273 Cyclohexaglycine 206 -, gel 55 Cyclols 194f,234, 270 -, gel penneation 170,241 -, anhydro- 196 -, HPLC 54 Cyclononapeptide 216 -, ion-exchange 113, 272 Cyclopeptides 13, 205-207, 216, 232, 234, -, liquid adsorption 55 239, 241, 271 Subject Index 289

Cyclopeptides, cytoprotective 216 Diazo- esters 27 -, homodetic/heterodetic 271 Dicarba analog, oxytocin 147 Cyclosporin A 21Of,211 Dicarbobenzoxy-L-cystine 64 Cyclotriglycine 206 Dicarbobenzoxylysine methyl ester 47 Cyclotripeptides 196 2,6-Dichlorobenzyloxycarbonyl group 67 Cyclotriproline 207 Dicyclohexylcarbodiimide (DCC,DCCI) Cyclotrisarcosine 207 87-94,97, 108 Cysteic acid 138 Diethyl chloroarsenite 92 Cysteine 62, 113 Dihydroflavin adenine dinucleotide (FADH) -, disulfide bonds 12 16 Cystine 5 Diisopropylcarbodiimide 108 -, reduction to cystein, Na in liquid Diketopiperazines 3,3,25,44,45, 110, ammonia 154 194, 195, 232 Cytochrome C 243 -, N-acetyl- 195 -, conformation 240 -, N-N' -diacetyl 45, 46 DANS peptides 115 4,4' -Dimethoxybenzhydryloxycarbonyl DANS amino acids 115 group 67 DCC (dicyclohexylcarbodiimide), coupling 3,5-Dimethoxybenzyloxycarbonyl group 68 87-89, 91, 93, 94, 97, 108 a,a-Dimethyl-3,5-dimethoxybenzyloxy• Deacetylation, enzymatic 26 carbonyl group (Ddz) 67 Deblocking, HCI in acetic acid 107 5-Dimethylamino-naphthalene-1-sulfonic -, trifluoroacetic acid in dichloromethane acid chloride (DANSyl chloride) 116 107 Dimethylformamide 82 Decapeptide, cyclic, antamanide 212 2,4-Dinitrochloro~e 114 Degradation, Edman 119, 120, 139, 167 2,4-Dinitrofluorobenzene 115, 138, 271 -,non~atic 270 2,4-Dinitrophenyl amino acids 115 -, stepwise peptide 117,266 2,4-Dinitrophenyl esters 87 Dehydro-amino acid 44 Dinitrophenylation 138, 140 Deletion peptides 110 Dipeptidase 17 Delicious peptide 189 2,2' -Dipyridyl disulfide 98 Delta-sleep-inducing peptide 188, 247 Displacement analysis 49 Deprotection, final 108 Disulfide bond,reaction 65 -, hydrogen fluoride 271 - bridges 14,72,73 Deprotonation 94 - chemistry 229 Depsipeptides 202,203,209,247 - formation from tritylthiols 170 -, cyclo- 195,224 - reduction, sodium in liquid ammonia 141, -, ionophoric cyclic 207 143 Derivatization, amino acids 113 1,4-Dithioerythrol (Cleland's reagent) 72 Dermorphins 186, 266 DNA 99,112,162,208 217, 220 -, recombinant technology 113,117,162 Detoxification 17 DNP amino acids 115, 115 Dextran, crosslinked (Sephadex) 55, 241 - peptides 115 Di-benzyloxycarbonyl-L-cystine 142 Dowex 50 Di-p-methoxytritylchloride 68 187 insipidus 150, 157 Diabetes mellitus 157, 171 N-N' -Diacetyldiketopiperazine 45, 46 Edman degradation 119, 139, 167 Diacylamine formation 46 - -, gas-phase 120 Diacylation 241 EEDQ 91,94 Diastereoisomers 104 Electron bombardment 129 -,~tion 233 Electrophoresis 4, 53, 273 -, separation 239 184f Diastereomers 55 Eledon aldrOllandi 185 290 Subject Index

Eledon moschata 185 Ficin 60 ~-Elimination 69, 70, 96 Field desorption technique (FD) 130 Elution analysis 49 Fischer projection 10 Enantiomers 54 Flavianate 144 Endorphines 187, 268 -, crystalline 141 60, 187 Flavianic acid (2,4-dinitro-l-naphthol-7- -, analogs 188 sulfonic acid) 48, 137 -, cyclic derivatives 188 Fluorenyl methyloxycarbonyl group (Fmoc) Enniatins 247 70, 71, 97, 107 -, cyc10depsipeptides 20f Fluorescamine 51 Enzymatic synthesis 229 Fmoc group 70, 71, 97, 107 Enzymes, affinity binding 57 Fonnate dehydrogenase 10 -, coupling with 99 Fonnylmethionine 208 Enzymology 68 Four-center condensation (4CC) 99,233 Epidennal growth factor 188 Fourier transfonn 132 Epidermin 223 Fraction collector, automatic 52 Ergobasine 194 Fragmentation of proteins 181 Ergot 3, 193f Freundlich-adsorption coefficients 49 - alkaloids 3, 193f, 265 Friedel-Crafts reactions 107 Ergotamine 193f Frontal analysis 49 -, thio- 198 Fungisporin 207 Ergotinine 193 Fusarium 20 Ergotismus gangraenosus 193 Ergotoxin 193 , insulin 162 ~-Galactosidase 162 ESR (electron spin resonance) 120, 127f 169f Ester chlorides, reactive 229 GaleriTUl marginata 221 Ester method 27 Gallbladder contracting honnone (chole- Esters, active 84ff, 108, 110, 111, 145, cystokinin) 165f, 168, 188, 238 161,167,206,235,240,241,243,264 113, 273 -, -, catalysis 243 Gastric inhibitory polypeptide (GIP) 168 -, -, catalysis, aminolysis 240 Gastric juice, releasing honnones (factors) -, -, coupling 87 172 -, -, insoluble 87 136, 165f, 188, 244 -, -, polymer-bound 111 -, little ("roinigastrin") 165 -, -, water-soluble 237 -, pyroglutamic acid 165 Ethanolamide 209 Gastrin II, tyrosin 165 Ethoxyacetylene coupling reagent 88, 241 Gelatine 28 Ethoxycarbonyl group 46 Gila monster 187 N-Ethoxycarbonyl group 69 Glucagon 167, 168, 171,233 Ethoxycarbonyl-2-ethoxy-l,2-dihydroquino- -, synthesis 168 line (EEDQ) 91 Glucose-dependent insulinotropic poly• N-Ethoxycarbonylphthalimide 70 peptide (GIP) 168 Ethylcarbonic acid mixed anhydride 91 Glumitocin (4-serine-8-glutamine oxytocin) Ethyl chlorocarbonate 81, 91 149 N-Ethylpiperidine 80 Glutamic acid 6, 48, 53, 66, 114 Exopeptidase 60 - -, poly-y-D- 236 D-Glutamic acid 236 Z-L-Glutamic acid a-methyl ester y- FADH 16 chloride 65 Fast bombardment (FAR) 130 Glutamine 62, 109, 142 Fast death factor 222 -, introducing 228 Fatty acids, gas chromatography 54 y-Glutamyl transpeptidase 17 Fibrin 1,4 15f, 15 Subject Index 291

Glutathione synthesis 64,65 Hydrazine 26, 116 Glutathione-S-transferases 16 Hydrazinoacids 234 Glutathione peroxidase 10 Hydrazinolysis 116,238 Glycine 5,38,45, 114,238 Hydrides, complex 117 Glycine ethyl ester 38 Hydrobromic acid 64 Glycopeptides 67,233 , catalytic 47, 66 Glycosylation 9, 113 -, pa.Iladium/platinum catalyst 63 N-Glycylglycineanhydride 196 -, transfer 236 Glycylglycine, X-ray crystallography 132 Hydrogen bonds, transannular, antamanide Glyoxalase 17 215 - reaction 17 Hydrogen fluoride,liquid 71, 107,238, Graft polymers 111 271 Gramicidins 103, 114, 203f, 204, 208, 209, Hydrogen iodide 65 239,244 Hydroiodic acid 46 -, antiparallel p-sheet 209 Hydrolysis,alkaline 105 -, biosynthesis 208 -, amino acids 113 -, cyclodimerization 271 -, - -, partial 113, 114 Growth hormone () 170f,229, -, enzymatic 56 242, 268 Hydrophobic interactions, side chains 12 Growth hormone releasing hormone 172, Hydroxamic acids 86 189 2-Hydroximinocyanoacetic acid 97 Guanidine derivatives 238 3-Hydroxy-3,4-dihydrobenzolriazine-4-one Gut peptides 189 94,98,109 3-Hydroxy-3,4-dihydroquinazoline-4-one 94,110 a-Halogen fatty acids 29 a-Hydroxyacyl1actames 194 Handle method 244 I-Hydroxybenzolriazole esters 92-94 Heavy-metal 72 I-Hydroxybenzolriazole (HOBt) 86,87,93, a-Helix 270 97,110,169 -, X-ray crystallography 132 a-Hydroxyisovaleric acid 201 Helodermin 187 Hydroxylamine derivatives 86 Helospectin 187 N-Hydroxyphthalimides 85, 86, 243 Hemoglobin 5 Hydroxyproline 5, 6, 35 -, X-ray crystallography 132 4-Hydroxyquinazoline-3-oxide 87 Hepatotoxic peptides 222 N-Hydroxysuccinimide 86,97 Heterodetic cyc10peptides 271 Hypertensin see Angiotensin - peptides 13 Hypertension, angiotensin 182, 183 Hexaglycine 30,31 Hypothalamus 171 Hexamethylsilazane 69 Hexapeptide, cyclic, NMR spectrum 126 Imidazoles 196 Hippopotamus, -vasopressin 150 -, acylation 87 Hippuric acid 25, 57 Immunopeptides 189 Hippmyl peptides 26 Immunosuppression, cyclosporins 211 6, 48, 49, 61, 62 Indole, tryptophan 95 Homodetic cyc10peptides 271 Infrared absorption 122f - peptides 13, 202 Inhibin 189 Hormone receptors,afflnity labeling 241 Insulin 44,72,73,77, 116, 138, 139, 147, Hormones, gastrointestinal 186, 232, 233, 157ff, 228-231, 233, 234, 243, 244, 266- 241,268,269 268,273,274 -, -, insulin-releasing effect 172 -, AlB chains 160 Hormones,peptide 136,232,243,267-269 -, amino acid sequence (bovine/ovine/por- -, -, antagonists 244 cine/human) 159 HPLC 54,61, 110, 169, 170 -, analogs 161, 234 Hydantoin 29 -, dinitrophenylation 158 292 Subject Index

InsuIin, disulfide bridges 158 Langerhans islet cells 157 -, human 161, 162 Lanthionine 113,222,223,223,234,235, -, intennolecular interactions 160 238 -,ovine 161 Lantibiotics 222f, 234 -, oxidation with performic acid 158 Lepiota mushrooms 221 -, oxidative sulfitolysis 160 Leuchs' substances 268 -, porcine 60 Leucine 2, 5, 35 -, -, desalanino 162 - anilide 57 -, proteolytic enzymes 159 -, L-y,&-dihydroxy- 217 -, recombination experiments 160 -, y-hydroxy- 218, 219 -, releasing effect, gastrointestinal honnones -, NMR 125 172 Leucokinins 189 -, 161 L-Leucylnonaglycine 31 -, sequence determination 2 Leukotrienes 17 -, structure 158f LH-RH see Luteinizing honnone releasing -, structure-3D 157, 159 honnone ", synthesis 160f LiAlH4 128 -, Zn complex 158 Liquid phase methods 234, 238 -, Zn, X-ray crystallography 132, 133 Litorea aurea 186 Ion-exchange chromatography 49,55 Litorea (Hyla) caerulea 166 Ion-exchange resins 111 Litorin 186 Ion conductance 209,210 LSD 194 Ionization, chemical 129 Luteinizing honnone releasing honnone Ionophores 21, 203, 214 (LH-RH) 172 -, artificial 203 --- -, analogs 239 Ion transport, membrane 230 Lycomarasmin 19f - -, valinomycin 201 Lysergic acid 194 Isobutylcarbonic acid mixed anhydrides 81 Lysine 6, 48, 49, 61 a-Isocyanatocarbonic acids 36 Lysine-vasopressin 85 Isoenzymes 273 Isoleucine 7, 81, 142 -, y,a-dihydroxy- 221 Macrocyclic lactones, formed by insertion -, NMR 125 194, 195 N-Isopenicillin 198-200 Macromolecules, soluble 247 Isopropyl chlorocarbonate 81 -, X-ray crystallography 132 Isotocin (4-serine-8-isoleucine oxytocin) Magainins 189 148 Malformin 19f Isotope dilution method 114 Mass spectrometry (MS) 113, 119, 120, Isovaleric acid acylamino acid mixed anhy- 128f, 213, 232, 273 drides 82 - -, derivatization 128 Isovaleryl chloride 82 - -, fragmentation 130 Isoxazole ring 90 Mastoparan 187 Isoxazolium salts 90 Melanocyte stimulating hormones (a-/~­ MSH) 163, 164 183f Mellitin 186 -, methionyl- 183 3-Mercapto-3,3-pentamethylene propionic 185 acid 148 Keteneimines 90 ~-Mercaptoethanesulfonic acid 229 Merrifield resin 105 Mesotocin (8-isoleucine oxytocin) 148 Lactam/lactone rings 13 Met- 60 y-Lactone 117 Metal ions, antamanide 215, 216 Lactones, macrocyclic, insertion reaction Methanolysis 129 194, 195 Methionine 7,95, 117 Subject Index 293 p-Methoxybenzyloxycarbonyl group 107 Nucleic acids 224 see also DNA and 2-D-Methyl-3-mercaptopropionyl-L-proline RNA 183 - -, sequencing 113 N-Methyl-acetamide 123 Nucleophile, auxiliary 93, 94 I-Methyl-histidine 15 Nucleotides 53 N-Methyl-peptides 129 N-Methylamino acids 96 Methyl esters 84 Oc~tide 30,31,35 - -, aminolysis 84 Ophthalmic acid 15, 18f - -, ammonolysis 84 Opioid peptides 60, 187f, 230, 237, 266 4-(Methylsulfonyl)-phenylsulfonylethyl• ORD (optical rotatory dispersion) 120, 121 oxycarbonyl (Mpc) group 243 Ornithine 205,235 Methy1sulfonylethyloxycarbonyl group Orthogonal combination 108 (Msc) 243 Osteoporosis 170 Microbiological assays 114 Ovalbumin 2,4 Microcystins 222f Oxazolidine-2,4-diones 36 Microcystis aeruginosa 222 5(4H)-Oxazolones 96 Molecular conformations, NOE effect 125 Oxytocin 77, 82, 83, 85, 1m, 127, 136, Morphine receptor 187 137ff, 154, 157, 167,188,231,232,236, Morphine-modulating peptide 189 242,243,246 Morpholine 70 -, 4-serine-8-glutamine (glumitocin) 149 168f -, 4-serine-8-isoleucine (isotocin) 148 MS see Mass spectrometry -,4-threonine-7-glycine 148 MSH 103, 163, 164 -, 8-isoleucine (mesotocin) 148 Myoglobin 5 -, analogs 146, 148:155 -, X-ray chrystallography 132 -, antagonist 148 -, antiarrhythmic action 149 -, carba analogs 147, 156 Nactins 203 -, carboxamide groups 148 Natriuretic factors 189 -, child birth 149 NCAs (N-Carboxyanhydrides) 35f, 37,41 -, chromatography 137 -, polymerization 38, 39 -, confonnation 147, 148 Neurohypophysis 137, 149, 157 -, cyclic structure 146 -, hormones 231,242,244 -, desamino 146-148, 155 Neuromedins 189 -, desamino-hydroxy 148 168,239 -, dicarba analogs 147, 156 -, VIP 168 -, dimers 147 Neurophysin complex 127, 148 -, disulfide bridge 146 Neurotoxic alkaloids 222 -, electropherograms 140 Neurotransmitters 267 -, electrophoresis 137 Newsprint reaction 220 -, glycyl- 148 Ninhydrin 51, 52, 113 -, honnonal activity 141 Nisin 222, 223, 267 -, killfish spawning reflex 149 2-Nitro-4,5-dirnethoxy-Z 68 -, lifespan of male rats 149 p-Nitrophenyl esters 85,108, 109, 196,205 -, NMR 148 o-N!trophenylsulfenyl group 68, 235 -, partial acid hydrolysis 140 p-Nltrothiophenyl esters 85, 244 -, partition chromatography 155 NMR 113, 120, 125f, 214, 229 -, receptors 146, 148, 156 -, 2D 127, 234, 242 -, synthesis 140f -, oxytocin 148 Oxytryptophan 217 NOE effect, molecular confonnations 125 Nomenclature/symbols 10, 11 Nonapeptides, blocked 143, 145 Pancreozymin 166 Nuclear Overhauser enhancement (NOE Papain 56,57,60 effect) 125 Parathyroid honnone (PTH) 169f, 238 294 Subject Index

Parathyroid hormone, human (PTHh) 169 Phenylalanine anilide 37 - -, pre- 169 Phenylalaninol 210 Partition coefficient 52 Phenylalanyl-phenylalanine anilide 37 Penicillamine 148, 154 N-Phenylcarbamoyl peptides 118 Penicillanic acid, 6-amino- 198, 200 Phenyl esters 85 Penicillin 123, 137, 154, 198f, 199, 199, - -, ammonolysis 85 201, 243, 267, 271 Phenylglycine, racemization 96 -, benzyl- 154 Phenylhydantoin 117, 118 -, biosynthesis 199 -, stepwise degradation 118 -, IR analysis 123 Phenylhydrazines 23 - ,iso- 198, 199 Phenylisocyanate 117 -, peptidoglycan inhibition 201 Phenylisopropyloxycarbonyl group 107 -, 241 Phenylisothiocyanate 118 -, thiazolidine-/3-1actam 198, 199 Phenylmercapturic acid 16 Penicillinase 154, 198 PHM-27 168 Pentafluorophenol 109 Phosphonium iodide 46, 65 Pentafluorophenyl esters 85, 87 Phosphopantetheine 208 Pepsin 56 Phosphoric acid mixed anhydride 92 Peptidases 56 Phosphorous acid, diesters 82 'Y-Peptide 15 Phosphoserine 240 Peptide bonds, cis/trans 11,12 Phosphotungstic acid 48 - -, trans, X-ray crystallography 132 Photolysis 68f Peptide formation, enzymatic 59 Phthaloyl group 202 Peptide synthesizer, automatic 68 Phthalyl group 69,70 Peptide-lipid interactions 230 Phyllomedusa bieolor 185 Peptides, biosynthesis 269 Phyllomedusa rhodei 186 -, channel-forming 267 Phyllomedusin 185 -, cyclic 13, 205-207, 232, 239, 241 185 -, cyclic microbial 208 Physalaemus fuscumaculatus 185 -, cysteine 270 Phytotoxins 19 -, dehydro- 246 Piperidine 70 -, gastrointestinal 236 Pituitary gland 137, 149, 163 -, hepatotoxic 222 - hormones 154, 155 -, membrane-active 270 Plastein 57 -, sulfur-containing 246 - reaction 59 -, venom 186f Pleated J3-sheet, X-ray crystallography 132 Peptidolipids 232 Poly-L-Iysine, CD spectra 123 Peptones 2 Polyacrylamide gels 4, 53 Performic acid 144 Poly alanine 40 Periodicity rule 4 Poly amino acids 37,38, 40f, 237, 268, 274 Permethylation 129 - -,IR 124 Permutites 49 Polyamino alcohols 128 211, 214, 216, 217 Polyaspartic acids 24 Phalloin 217 Polyethyleneglycol 234 -, synthesis 218, 219 Polyglutamic acids 40 212, 216, 217, 221 Polyglycines 38, 40 -, F-actin filament stabilization 218 - esters 38 Phenols 87 Polylysines 40 Phenylthiohydantoins (PTHs) 119,119 Polymer-bound active esters 111 S-Phenyl-N-acetyl-L-cysteine 16 Polymeric supports 109, 110 Phenyl-propyl-2-oxycarbonyl group 66 - -, insoluble 85, 103, 145, 161, 240 Phenylalanine 6,49, '20, 145 Polymeric reagents 270 -, NMR 125 Polymers, soluble 111 -, UV 121 Polymyxins 242 Subject Index 295

Polynucleotides 112 Racemization 61, 81, 91, 93-96, 233, 244, Polypeptides 113 272 -, definition 2 -, prevention through additives 234, 240 -, IR 124 -, proton abstraction 89 Polyprolines 40 -, suppressing additives 97 Popcorn resin 104 -, urethane-type blocking groups 65 Posttranslational processing 186 Radicals 127 -- modification 9, 113 Radioimmunoassay 220 -- -, glutamic acid 9 Raleigh scattering 123 Pr~ohormones 181, 189 Ramachandran plot 12, 236 Presomatostatin 171 Raman spectra 122f Pro-opiocortin 188 Rana pipiens 186 Prohormones 181, 189 Ranatensin 186 Proinsulin 161, 162, 234 Raney nickel 139 - to insulin 163 Receptor-agonist interactions 242 Proline 6, 96, 235 Recombinant DNA technology 113, 117, -, 2,3-trans-3,4-trans-3,4-dihydroxy-L- 162 218 Reduction, electrolytic 26 -, 4-cis-hydroxy- 217 Reinecke acid (tetrarhodanatodiaminchromic -, 4-trans-hydroxy- 221 acid) 48 N-Prolyl-cyclo-dialanine 196 Releasing factors (releasing hormones) Propen-1-yloxycarbonyl group 67 17lf, 246, 266 Protecting groups 62 Releasing hormones (releasing factors) - -, amino- 29 171f, 246,266 - -, carboxyl 70 Renin 181, 182 - -, sulfhydryl 235 -, inhibitors 182, 183, 246 - -, urethane-type 97 Resins, "popcorn" 104 N-Protecting groups 105 Resins, Merrifield 105 S-Protecting groups 72 Resonance stabilization 11 Proteinases 56, 58 Restriction enzymes, insulin production Protein cleavage, non-enzymatic 274 162 - crystals, X-ray crystallography 132 Rhodanilic acid 48 - fragmentation 181 Ribonuclease A 41, 237, 239, 243, 269, -, protoplasmic 1 272 - synthesis 59 -, structure elucidation 51 Proteolytic enzymes 56, 62, 99 -, synthetic 170 Protonation 94 -, IH-NMR spectrum 127 Protoplasmic proteins 1 -, NMR 125 PTH () 169f Ribosomes, protein synthesis 59,207 Purification, amino acids 113 Rigin 189 -, peptides 237 RNA polymerase 221 Purines 266 RNA, messenger 113,208 Pyrazole 87 -, transfer 59, 207 Pyridinium chloride 240 Rotation, specific 144 Pyroglutamic acid, gastrin 165 Ruhemann's purple 51 Pyroglutamyl residue 228 - -, eledoisin 185 Pyrrolinones 52 S-peptide 41,237,271 S-protein 41 Safety-catch 70 Salicylic acid 197 Quinoline 91 Saponification resistance, tert-butyl group Quinoxolines 224 66 296 Subject Index

Sarcosine 206, 224 184, 185, 232 186 Sulfhydryl protecting groups 146, 147,235 Scorpion toxins 240 Sulfitolysis 72, 72 Secolactone 218 Syntheses, enzymatic 57,59 Secretin 85, 136, 167f, 231, 234, 241, 243, 246,265,269 Tachikinins 186 -, biosynthesis in 167 Tea-bag method 111 -, condensation of segments 167 Tetraethyl pyrophosphate 92 -, Edman degradation 167 - pyrophosphite 82, 143 -, glucagon homology 167 Tetraglycine ethylester 27, 38 -, stepwise synthesis 167 2,2,5,5-Tetramethylpyrrolidine-l-oxide 127 -, fragmentation 167 Tetrapeptides, cyclic 207 Selenocysteine 10 Tetrazole 87 Semisynthesis, protein 242 TFA-amino acid 70 Sephadex 55,241 -- esters 54 Sequenator, automatic 119, 120, 229 TFA-peptides 70 Sequence peak ions 129 Theobromine 232 Serine 6,61,62,67,238 Thermolysin 60 -, phospho- 240 Thiazolidine-p-Iactam 154 D-Serine 217 -, penicillin G 198, 199 4-Serine-8-glutamine oxytocin 149 Thiazolidine-azlactone structure 154 Serratamolide 195,196 N-Thiocarbamic acid anhydrides (TeAs) p-Sheet, antiparallel, gramicidin 209 41 Silico-organic compounds 68f Thioergotamine .198 Silk fibroin, X-rays 3 Thioester crosslinks 217 Silver glycinate 79 Thioether amino acids 223 220 - bridge 218 Silyl esters 69 Thiol esters 208 N-Silyl group 69 - function 230 S-Silyl compounds 69 Thioltransferases 15 Silymarin 220 Thiolysis 72 Simultaneous multiple peptide synthesis Thionyl chloride 29 (SMPS) 111 Thiophenol 84, 87 Sodium dodecylsulfate 4, 53 Thiophenyl esters 78 Solid-phase peptide synthesis 103ff, 234, - -, aminolysis 85 238,245,247 Thiorhodanides 72 --- -, automation 109 Thiostrepton 244 --- -, Letsinger's approach 105 Thiotemplate mechanism 208, 211, 223 --- -, Merrifield's approach 106, 108 Thioureido compounds 118 Solubility product method 48, 114 Threonine 7, 61, 62, 67, 238 Somatostatin 17Of, 229, 242, 268 -, tert-butyl ester 162 -, bicyclic analog 171, 171 D-Threonine 217 -, carba analogs 171 inhibitors 236 -, human 172 Thyrocalcitonin 170 -, pre- 171 Thyroid hormones 169f -, solid-phase synthesis 171 Thyroliberin (TRHII'RF) 172 Spectroscopic methods 114, 120f Thyrotropin releasing hormone (fRH/fRF/ Spin-spin coupling 125 thyroliberin) 172 Staphylococcus epidermidis 223 Toadstools see Amanita Stereoisomers, FIscher convention 23 N-p-Toluenesulfonyl group 107 , adrenal cortex 163 Toluenesulfonyl residue 64 Strategy, stepwise 103 p-Toluenesulfonyl-L-glutamic acid 142 Strychnine alkaloids 36 p-Toluenesulfonyl-L-pyroglutamyl-L-asp- Styrene/divinylbenzene copolymers 104 aragine 142 Subject Index 297

2-(4-Toluenesulfonylmethyl)ethoxycarbonyl Ultracentrifuge 4 group 70 Uperolein 185 p-Toluenesulfonyl-pyroglutamic acid 142 Urethane 81 Tolypocladium injlatum 211 Urethane-type blocking groups 65 Tosylamino acid chlorides 229 Urogastrone 188 Transesterification 230, 240 UV spectroscopy 120f -, base-induced 88 Transpeptidation 60 TRH see Thyrotropin releasing hormone Tri-p-methoxytritylchloride 68 Vaccines, synthetic 189 1,2,4-Triazole 87 Valine 6,81 Trichloroacetic acid 68 -, NMR 125 2,4,5-Trichlorophenyl esters 85, 109 Valinomycin 20lf, 201, 247 Trichoderma viride 210 Valinomycin-K+ complex 201, 202, 214 TricluJderma polysporum 211 van Dyke protein 148 Triethyl phosphate 247 Vasoactive intestinal peptide (VIP) 168, - phosphite 247 189,243 Trifluoroacetic acid 54, 64, 67, 70, 107, Vasopressin 136, 149ff, 154, 157, 188 108, 110, 119, 164, 233 -, agonists 151 Trifluoroacetyl-L- cyclohexyl -, amino acid sequence 155 esters 55 -, analogs 150, 151,241 Trifluoroacetylation 54 -, antidiuretic effect 149, 151 N-Trifluoroacetyl derivatives 273 -, arginine- 149, 150, 152 Trifluoroacetylpeptide esters 129 -, arginine-,ureido group 150 - methyl esters 129 -, chromatography 137 Trifluoromethanesulfonic acid 107 -, citrullin analog 150 Triglycine, IR spectrum 124 -, 1-desamino-8-D-arginine 150 Triglycine azide 206 -, diabetes insipidus 150 Trimethylchlorosilane 69 -, Edman degradation 155 Trimethylfluorosilane 69 -, effect on memory 152 Trimethylsilyl group 69 -, electrophoresis 137 Trimethylsilylethyl esters 69 -, 8-homolysine 150 Triphenylmethyl group 67, 71, 205 -, 8-homonorleucine 150 Triphenylphosphine 98 -, 8-E-hydroxynorleucine 150 Trityl group 68, 232 -, inhibitors 151 N-Trityl compounds 68 -, lysine- 85, 147, 149, 150 S-Trityl-cysteine 71 -, 2-(I-mercaptocyclohexyl) acetic acid 151 Truncated sequences 110 -, 8-ornithine 150 Trypanothione 18 -, receptors 148 Trypsin 56,57,59, 117, 151, 157, 162, -, -, electrostatic interactions 150 167, 182, 183 Vasotocin 152 Tryptathionine 217 -, arginine- 152 Tryptophan 6, 49, 120 -, lysine- 15 -, indole 95 Venom peptides 186f -, NMR 125 Vespulakinin 187 -, UV 121 Vibrational spectroscopy 122f Tryptophan synthetase 162 Vinyl esters, ammonolysis 85 Tryptophillin 186 VIP 168, 189, 243 Tuftsin 189 217 Tyrocidines 203,204,207 Vitamin B'2 267 Tyrosine 2, 5, 49, 61, 62, 120, 145 -, NMR 125 -, UV 121 Walden inversion 29 Tyrothricin 203, 207 Woodward's Reagent K 90 298 Subject Index

X-ray diffraction analysis 4, 131ff, 214, X-rays, silk fibroin 3 215,221,267,268 - -, D-isoleucine 10 Z-chloride 63 - -, single crystals 125 Zn-insulin 158, 160 - -, valinomycin 202 -, X-ray crystallography 132 M.Bodanszky, Case Western Reserve University, Cleveland,OH Principles of Peptide Synthesis 1984. XVI, 307 pp. (Reactivity and Structure, Vol. 16) Hardcover DM 160,- ISBN 3-540-12395-4

Contents: Introduction. - Activation and Coupling. - Reversible Blocking of Amino and Carboxyl Groups. - Semipermanent Protection of Side Chain Functions. - Side Reactions in Peptide Synthesis. - Tactics and Strategy in Peptide Synthesis. - Tech• niques for the Facilitation of Peptide Synthesis. - Recent Developments and Perspectives. - Author Index. - Subject Index.

M.Bodanszky, A.Bodanszky, Case Western Reserve University, Cleveland,OH The Practice of Peptide Synthesis 1984. XVII, 284 pp. (Reactivity and Structure, Vol. 21) Hardcover DM 168,- ISBN 3-540-13471-9

Contents: Introduction. - Protecting Groups. - Activation and Coupling. - Removal of Protecting Groups. - Special Procedures. - Models for the Study of Racemization. - Reagents for Peptide Synthesis. - Appendix. - Author Index. - Subject Index. A textbook resulting from years of experience

M. Bodanszky, Princeton, NJ Peptide Chemistry A Practical Textbook 1988. XII, 200 pp. 2 figs. 5 tabs. Softcover DM 48,• ISBN 3-540-18984-X

Contents: Introduction. - Structure Determination: Amino Acid Analysis. Sequence Determination. Secondary and Tertiary Structure. - Peptide Synthesis: Formation of the Peptide Bond. Protection of Functional Groups. Undesired Reactions during Synthesis. Racemization. Design of Schemes for Peptide Synthesis. Solid Phase Peptide Synthesis. - Methods of Facilitation. Analysis and Characterization of Synthetic Peptides. - Subject Index.

T. Wieland, Heidelberg Peptides of Poisonous Amanita Mushrooms 1986. XIV, 256 pp. 78 figs. (Springer Series in ) Hardcover DM 198,- ISBN 3-540-16641-6

Contents: Introduction. - Mushrooms Causing Death in Rare Cases. - Deadly Poisonous Amanita Mushrooms and Their Constituents. - Toadstools Accumulating Amatoxins. - Poisoning by Amatoxins. - Two Centuries of Amanita Research. - Recognition, Isolation and Characterization of the Peptide Toxins. - The Chemistry of the Amatoxins, Phallotoxins and Virotoxins. - Molecular Pathology ofthe Amanita Peptides. - Non-Toxic Peptides from Amanita phalloides. - Phallolysin. - Retrospectives and Outlook. - References. - Subject Index.