Leonidas Zervas | |
|---|---|
Λεωνίδας Ζέρβας | |
| Born | (1902-05-21)21 May 1902 Megalopolis, Greece |
| Died | 10 July 1980(1980-07-10) (aged 78) Athens, Greece |
| Nationality | Greek |
| Alma mater | University of Athens University of Berlin |
| Known for | Carboxybenzyl protecting group,Peptide synthesis |
| Spouse | Hildegard Lange |
| Awards |
|
| Scientific career | |
| Fields | Organic chemistry |
| Institutions |
|
| Thesis | Über die Aldehydverbindungen der Aminosäuren[a] (1926) |
| Doctoral advisor | Max Bergmann |
| Notable students | Panayotis Katsoyannis Iphigenia Photaki |
Leonidas Zervas (Greek:Λεωνίδας Ζέρβας,pronounced[leoˈniðasˈzervas]; 21 May 1902 – 10 July 1980) was aGreekorganic chemist who made seminal contributions inpeptide chemical synthesis.[1][2][3][4] Together with his mentorMax Bergmann they laid the foundations for the field in 1932 with their major discovery, theBergmann-Zervas carboxybenzoxy oligopeptide synthesis which remained unsurpassed in utility for the next two decades.[1][2] Thecarboxybenzylprotecting group he discovered is often abbreviatedZ in his honour.[1]
Throughout his life Zervas also served in many important posts, including President of theAcademy of Athens or brieflyMinister of Industry of Greece.[2][4] He received numerous awards and honours during his life and posthumously, such as Foreign Member of theUSSR Academy of Sciences or the first Max Bergmann golden medal.[1][2][3][5]
Zervas was born in 1902 in the rural town ofMegalopolis inArcadia, southern Greece.[3] He was the first of 7 children of lawyer and parliamentarian Theodoros Zervas with Vasiliki Zerva (née Gyftaki).[2][3] After finishing secondary education at the local Gymnasion ofKalamata in 1918, he went to study Chemistry at theUniversity of Athens.[1][2] Before finishing his studies there, he moved to Berlin in 1921 where he graduated with a degree in chemistry from theUniversity of Berlin in 1924.[1][2][4]
Under the supervision ofMax Bergmann, he finished his doctoral thesis on the reactions of amino acids with aldehydes and was awarded hisDr. rer. nat. from the University of Berlin in 1926.[4] He proceeded to work with Bergmann in theKaiser Wilhelm Institute for Leather Research inDresden, of which Bergmann was the founder and director.[1] From 1926 to 1929 Zervas was a research associate and eventually rose to head of the organic chemistry division and vice-director of the institute (1929–1934).[1][2] It was at this period that the two men developed the Bergmann-Zervasoligopeptide synthesis which brought them international fame within academic circles.[1][3]
Zervas, by that point a close personal friend of Bergmann, decided to follow the latter to the US in 1934 after Bergmannemigrated from Nazi Germany in 1933 under pressure due to his Jewish origin.[1][3] In New York, Zervas spent 3 years as lecturer and researcher at theRockefeller Institute for Medical Research.[1][4]
In 1930, he married Hildegard Lange, and they remained together until his death.[2][3]
After his Berlin, Dresden and New York years, Zervas decided to return to Greece in 1937.[3] He was immediately appointed full Professor of Organic Chemistry and Biochemistry at theAristotle University of Thessaloniki in recognition of his distinguished international work.[2][3] He stayed in this position until 1939, when he was invited to the Professorship of Organic Chemistry at theUniversity of Athens and also appointed director of the Laboratory of Organic Chemistry of the same institution.[2] He continued conducting research, despite the severe limitations he often faced from the lack of equipment and funding.[2] Concurrent to research, Zervas taught organic chemistry, oversaw the laboratory and guided many generations of young chemists as doctoral advisor for the 29 years he held the post at the University of Athens.[1][2]
During theAxis occupation of Greece Zervas played an active part in theGreek Resistance as a member ofEDES; he was imprisoned twice, first by the Italian and then by the German occupying forces, and his laboratory was destroyed.[2][3] Following the liberation of Greece, Zervas managed to secure a small part of theAmerican postwar aid for repairs in the University of Athens and theAthens Polytechnic, and thus rebuilt his laboratory in 1948–1951.[2]
In the following years, guided by a sense of personal and professional duty, Zervas voluntarily took on a variety of responsibilities within the Greek state.[2] At his own insistence, he never got paid for these posts and kept receiving only his professorial salary.[2][3] Some notable positions he held in chronological order until 1968 include:[4]
The democratic ideals of Zervas made him a target of themilitary junta established in 1967, which removed him from his position in the University of Athens in 1968 after almost three decades of dedicated research and teaching.[2][3] In response, theAcademy of Athens of which Zervas had been a member since 1956 elected him as its president in 1970.[3] After his term as President of the Academy, Zervas retired in 1971.
With therestoration of democracy in 1974, Zervas was able to contribute once more to research and educational policy.[3] As previously, refusing to take a salary for these positions, he served a second time as the President of the Greek Atomic Energy Commission (1974–1975) and then as the President of the National Hellenic Research Foundation (1975–1979).[2][3][4]
Zervas had suffered from periodic issues with respiratory health throughout his adult life, but in his final years the situation deteriorated.[2] The extended use ofphosgene in his research has been implicated as the cause of this chronic pulmonary disease.[3] He showed perseverance and a pleasant attitude despite his health issues, continuing to attend meetings of the Academy of Athens until the very end of his life.[3] This came in the summer of 1980 after an acute pulmonary episode, which lasted three weeks before he died at the age of 78.[2]
The enduring contributions of Zervas were made together with Bergmann and involved the first successfulsynthesis of substantial lengtholigopeptides.[1] They achieved this using thecarboxybenzyl amineprotecting group for the masking of theN-terminus of the growing oligopeptide chain to whichamino acid residues are added in a serial manner.[1][6] The carboxybenzyl group discovered by Zervas is introduced by reaction withbenzyl chloroformate, originally in aqueoussodium carbonate solution at 0 °C:[6]
The protecting group is abbreviatedCbz or, in honour of Zervas, simplyZ.[1] The typical route for deprotection involveshydrogenolysis under mild conditionse.g. with hydrogen gas and a catalyst such aspalladium on charcoal.[6]
The discovery of the Bergmann-Zervas synthesis has been characterised as "epoch-making"[1] as it allowed the advent of controlled synthetic peptide chemistry, completing the work started in the early 20th century by Bergmann's mentorEmil Fischer. Previously impossible to synthesise oligopeptides with a highly specific sequence and reactiveside chains were consequently produced in the 1930s by Bergmann and Zervas.[1][2] The ability of Z-protection to prevent racemization of activated derivatives of the protected amino acids and the importance thereof were also noted by the two chemists.[1][6]
Indeed, their method became the standard in the field for the following two decades until further developments in the early 1950s with the introduction of mixed anhydrides (e.g. theBoc group).[1]
Zervas continued his research on peptide synthesis in New York and later in Greece.[2] The first topic of his research once in Greece was the synthesis ofN- orO-phosphorylated amino acids, in which he demonstrated the utility of dibenzyl chlorophosphonate.[1] He continued his efforts on the development of new methods within peptide chemistry, including the introduction of theo-nitrophenylsulfenyl (NPS) amino protecting group and peptide synthesis usingN-tritylamino acids.[1]
One of the major issues which occupied his interests was the chemical synthesis ofinsulin after its characterisation byFrederick Sanger (1951).[1] The insulinpeptide hormone features two protein chains cross-linked bydisulfide bridges fromcysteine thiols. For this reason, Zervas undertook a systematic study on asymmetric cysteine-containing peptides.[1][2] In his attempts he introduced new mercaptan protecting groups (e.g.trityl,benzhydryl orbenzoyl), which finally made it possible to produce disulfide bridges in a controlled manner.[1] This was a triumph for peptide chemistry in the lab, but could not be possibly scaled to industrial procedures. Building on this work, the first complete synthesis of insulin was simultaneously achieved in 1963 inRWTH Aachen University byHelmut Zahn and in theUniversity of Pittsburgh byPanayotis Katsoyannis, a student of Zervas.[1] Further work on asymmetrical cysteine polypeptides was also done in Athens byIphigenia Photaki, another student of his.[1][3]
Overall, the research work of Zervas spans across six decades (1925–1979) and amounts to 96 publications in international chemistry journals.[2]
The scientific work of Leonidas Zervas had a global resonance and his contribution was recognised by multiple awards throughout his life.[1][2][3][4] In 1960 he received anhonorary doctorate from theUniversity of Basel on the occasion of the university's 500th anniversary, upon recommendation ofHans Erlenmeyer and Nobel laureateTadeusz Reichstein.[1][3] In 1969 he was bestowed honorary membership of the American Society of Biological Chemists.[1][2] In 1976 he was conferred theOrder of Scientific Merit [ro] (1st class) by theSocialist Republic of Romania.[2] In the same year Zervas was made Foreign Member of theUSSR Academy of Sciences, an indication of the great respect for his work in theEastern Bloc, too.[2][3] The Max-Bergmann-Kreis company of German peptide chemists planned to present Zervas with the first Max Bergmann golden medal for peptide chemistry in 1980, but his sudden death necessitated a posthumous award ceremony.[3]
In honour of Zervas, a commemorativebust has been unveiled in his birthtown Megalopolis in 1991[5] and the main conference hall of theNational Hellenic Research Foundation is called the "Leonidas Zervas amphitheatre".[7]
The European Peptide Society has established theLeonidas Zervas Award "in commemoration of his outstanding contributions to peptide science", awarded biennially since 1988.[8] The award is given to the "scientist who has made the most outstanding contributions to the chemistry, biochemistry and/or biology of peptides in the five years preceding the date of selection".[8]
