ZERVAS, LEONIDAS

(b. Megalopolis, Greece, 21 May 1902; d. Athens, Greece, 10 July 1980)

organic chemistry.

After completing secondary school in Kalamata in 1918, Zervas spent two years as a student of chemistry at the University of Athens. In 1921 he moved to Germany and continued his studies at the University of Berlin, where he received his D. Phil. degree in 1926 for the dissertation Über die Aldehydverbindungen der Aminosäuren. It was based on work he did at the Kaiser Wilhelm Institute for Leather Research in Dresden, under the supervision of Max Bergmann, its director.

Zervas then became a research associate at the Dresden institute, and in 1929 was appointed its deputy director and head of the organic chemistry section. In 1933 the Nazis forced Bergmann to resign as director; after finding a haven at the Rockefeller Institute for Medical Research in New York, he secured the help of the Rockefeller Foundation in bringing Zervas to his new laboratory. Zervas resigned his post in Dresden, remained in New York for two years (1934–1936), and then returned to Greece. In 1937 he was appointed professor of organic chemistry and biochemistry at the University of Thessaloniki. Two years later he became professor of organic chemistry at the University of Athens; he reached emeritus status in 1968. In 1930 Zervas married Hildegard Lange.

The outbreak of World War II, the German occupation of Greece, and the civil war that followed liberation prevented Zervas from fully developing his research program until about 1950. Despite an interruption during the rule of the Greek military junta, when Zervas was dismissed from his professorship, he organized an outstanding laboratory from which there came not only important chemical contributions but also able young men and women who later gained recognition for their independent work. Zervas’ research career is therefore marked by two productive phases: the period 1926 to 1936, when he was associated with Bergmann in Dresden and New York, and that after about 1950, when he directed his laboratory in Athens.

Most of Zervas’ papers of the first period appeared with Bergmann’s name as the first author, but there can be little doubt that from the beginning of their association, Zervas made numerous original contributions. Initially his research dealt with the chemistry of amino acids. For example, in 1927 he demonstrated the chemical transfer of the amidine group of arginine to glycine; this “transmidination” reaction was later shown by others to be an enzymecatalyzed process in biological systems. In 1930 Zervas turned to sugar chemistry. One of his contributions was the synthesis of I-benzoylglucose by the hydrogenolysis of its 4, 6-benzylidene derivative with palladium black as the catalyst. This procedure for the gentle removal of benzyl groups had been introduced during the 1920’s, and its use in Bergmann’s laboratory led to the invention of an important new method for the synthesis of peptides. The method involved the protection of reactive groups in amino acids (amino, carboxyl, hydroxyl) by means of the “carbobenzoxy” group (more accurately, benzyloxycarbonyl; abbreviated Z). Selective removal of the Z-group after the assembly of the protected amino acid units had been completed gave the desired free peptides.

The publication in 1932 of the Bergmann-Zervas paper “Über ein allgemeines Verfahren der Peptidsynthese” marked a new stage in the development of peptide chemistry, a field first explored systematically by Emil Fischer from 1901 to 1909. Fischer’s procedure for the synthesis of peptides had many limitations, which were overcome by the introduction of the carbobenzoxy method. In rapid succession, from 1933 to 1934, there appeared a series of papers from the Dresden institute describing the synthesis of many hitherto inaccessible peptides containing amino acid units (aspartic acid, glutamic acid, lysine, arginine) with reactive side-chain groups, thus showing the general applicability of the method. Moreover, an important advantage of the use of Z-amino acids was that they were relatively resistant to racemization.

After his return to Greece in 1936, Zervas worked on the synthesis of phosphorylated amino and hydroxy compounds, a subject he had begun to explore in Dresden through the use of derivatives of dibenzylphosphoric acid. However, this promising approach was developed elsewhere from 1939 to 1950, a time when conditions in Greece prevented Zervas from continuing his research. After he was able to resume work, he published several papers on the use of dibenzylphosphorochloridate in synthetic reactions, but in succeeding years the main efforts in his laboratory were directed to the development of new methods in the peptide field.

During the 1950’s peptide chemistry gained wider interest as a consequence of the discovery that many antibiotics and hormones are peptides. Moreover, the elucidation of the amino-acid sequence of insulin by Frederick Sanger offered a challenge to peptide chemists to synthesize this protein hormone. Of particular interest was Sanger’s finding that insulin consists of two peptide chains joined by disulfide bridges involving cysteinyl units of the separate chains. Zervas undertook a systematic study of the synthesis of such structures and developed methods for making asymmetric cystine peptides. New protecting groups for the sulfhydryl group were introduced, among them the trityl (triphenylmethyl), diphenylmethyl, and benzoyl groups; the selective removal of these groups permitted the formation of the desired disulfide bridges. Also, Zervas developed the use of o-nitrophenylsulfenyl chloride (NPS-CI) for the protection of amino groups; the lability of the NPS group under mildly acidic conditions made it a valuable adjunct to the available tools of peptide synthesis.

Except when the political situation in Greece prevented it, Zervas was active in the general development of science in his country. He served as chairman of the Greek Commission for Atomic Energy (1964–1965) and later helped to organize the Greek National Research Foundation, of which he as president from 1974 to 1979.

BIBLIOGRAPHY

I. Original Works. A list of Zervas’ scientific papers before 1972 is given with the biographical article by P. G. Kastsoyannis, in The Chemistry of Polypeptides (New York, 1972), 1–20.

II. Secondary Literature. Only brief accounts of Zervas’ life have appeared. Especially noteworthy is the one by P. G. Katsoyannis (see above). An excellent summary of the contributions of the Zervas group to the synthesis of asymmetric cystine peptides is provided by his collaborator Iphigenia Photaki on pages 59–85 of that volume.

Joseph S. Fruton