In memory of Roger W. Jeanloz, a pioneer glycobiologist (1917–2007)
2 Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
3 Department of Pediatrics, School of Medicine, University of Pennsylvania and Children's Hospital of Philadelphia, Philadelphia, PA, USA
4 National Institute for Medical Research, Mill Hill, London, UK
1 To whom correspondence should be addressed: e-mail: nathan.sharon{at}weizmann.ac.il
|
Roger William Jeanloz, who passed away on September 12, 2007, a few weeks short of his 90th birthday, was among the earliest pioneers in the field of Glycobiology. He made seminal contributions to the subject and trained a number of leaders in the field. Among others, he was one of the prime organizers in the 1950s of the Glycosaminoglycans, Glycoproteins and Glycolipid Group (known as the 4Gs group), later named the Society of Complex Carbohydrates and eventually the Society for Glycobiology, and served as its President in 1974.
 |
From glycogen and deoxy sugars to complex carbohydrates |
|---|
 Top From glycogen and deoxy... Applications of methylation...Rare amino sugars, glycolipids,...Editor, symposia organizer, and...Dedicated teacher, avid... |
|---|
Jeanloz was born on November 3, 1917 in Berne, Switzerland, to a French mother and a Swiss-German father. He was brought up in French-speaking Geneva where he pursued classical studies emphasizing Greek and Latin at College Calvin. In 1936 he was awarded the B.S. degree and in 1941 a Diploma in Chemical Engineering from the University of Geneva, where he studied organic chemistry and biochemistry. His keen interest in science and research began in 1941 when Professor Kurt H. Meyer, well known for his pioneering studies on cellulose and starch, accepted him as a doctoral student. In Meyer's laboratory Jeanloz investigated glycogen and at the same time served as a head instructor for Organic Chemistry. In 1943, after being awarded the D.Sc. degree, he was appointed as a research associate, first with Meyer and then with Professor Tadeusz Reichstein, Nobel Laureate for his work on steroid hormones. With Reichstein, Jeanloz studied the chemistry of deoxy sugars, some of which are constituents of the above hormones. He spent 1 year (1946–1947) in Canada as a research associate at the University of Montreal and then moved to the United States where he worked for 1 year as a senior research fellow in the National Institutes of Health laboratory of the noted carbohydrate chemist, Claude S. Hudson. The following 3 years were spent at the Worcester Foundation for Experimental Biology, then under the direction of Gregory Pincus, working on steroid hormones.
In 1951, Jeanloz was invited by Dr. Walter Bauer, chief of the Medical Services and the Arthritis Unit at the Massachusetts General Hospital, to become a member of the Robert W. Lovett Memorial Group for the Study of Crippling Diseases and to organize a laboratory for the study of the chemical structure of the polysaccharides of connective tissue and of related biochemical problems. Ten years later, he was appointed as Head of the newly formed Laboratory for Carbohydrate Research of the Lovett Group, and in 1969 as Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He held these positions until his retirement, but continued to be active in research and teaching thereafter. It was in the Carbohydrate Research laboratory that Jeanloz made his major contributions to our knowledge of the structure, biosynthesis, and function of complex carbohydrates. Most prominent among these were the elucidation of glycosaminoglycan structures, chiefly by methylation analysis; synthesis of rare amino sugars; establishment of the structure of the disaccharide constituent of the bacterial cell-wall peptidoglycan; providing the foundation for structural studies of the carbohydrate moieties of N- and O-linked glycoproteins and synthesis of many of the glycopeptide constituents of glycoproteins; detailed structural analysis as well as synthesis of several of the dolichyl sugar phosphates involved protein glycosylation; and characterization of glycans accumulated in lysosomal storage diseases and the actions of catabolic glycosidases. In addition, analysis of TA-3 glycoprotein initiated in his laboratory led to the most detailed investigation of any tumor-related glycoprotein examined at the time.
|
Applications of methylation analysis |
|---|
|
TopFrom glycogen and deoxy...Applications of methylation...Rare amino sugars, glycolipids,...Editor, symposia organizer, and...Dedicated teacher, avid... |
|---|
Before joining the Lovett Group, Jeanloz devoted considerable efforts to understanding the periodate-oxidation reaction and used it to study the structure of hyaluronic acid and related glycosaminoglycans. It rapidly became evident to him that this method, as was the case in the successful determination of the structure of simpler polysaccharides (glycogen or starch), required supplementation with other methods, particularly the methylation technique. The latter technique had already been attempted in the field of glycosaminoglycans, but without success. The main difficulty resided in the fact that the degradation of a methylated polysaccharide, made of repeating units of hexosamine and uronic acid with different linkages, could give rise to a large number of mono-, di-, and tri-O-methylated monosaccharides. It was therefore necessary to synthesize all of the reference substances and to separate and identify them in artificial mixtures. Jeanloz was encouraged in this long and arduous task, which required gram quantities of starting materials, by the knowledge that if shown to be efficient, the method could be applied not only to the elucidation of the structure of the glycosaminoglycans but also to other classes of complex carbohydrates. The methylated derivatives served as the basis of elegant studies in which Jeanloz and his colleagues unequivocally established the structure of hyaluronic acid, dermatan sulfate, and chondroitin 4-sulfate. They also clarified many confusing issues, including the position of the sulfate groups in these polymers. In the course of this work they proved that dermatan sulfate contained L-iduronic acid, a sugar not known before to occur in nature.
The methylated substances were in such demand by other laboratories as reference compounds that one research assistant worked full time solely to replenish supplies. Jeanloz was greatly helped in this synthetic approach, which took 10 years to accomplish, by a large number of associates; prominent among them was Pierre J. Stoffyn, who joined his group in 1953 and stayed until 1961. One of the many results of their productive collaboration was the Stoffyn and Jeanloz method for identification of hexosamines by ninhydrin degradation to the corresponding pentoses, which is still the simplest method to distinguish between glucosamine and galactosamine.
|
Rare amino sugars, glycolipids, and N-glycoproteins |
|---|
|
TopFrom glycogen and deoxy...Applications of methylation...Rare amino sugars, glycolipids,...Editor, symposia organizer, and...Dedicated teacher, avid... |
|---|
The synthetic studies of Jeanloz led to the solution of many questions in carbohydrate chemistry, especially those related to amino sugars. Resulting from these studies was the synthesis of several amino sugars, some of which (e.g., D-gulosamine) had been shown to be constituents of aminoglycoside antibiotics, such as streptothricins, and others that at that time were not known to occur in nature (e.g., D-allosamine and D-talosamine). Bacillosamine (2,4-diamino-2,4,6-trideoxy-D-glucose), another rare amino sugar, was first isolated in the Jeanloz laboratory from a bacterial polysaccharide; it has recently been identified as a constituent of the carbohydrate–peptide linking group of glycoproteins of eubacterial pathogens and is currently attracting considerable interest.
A number of the central themes of current glycoconjugate research can be traced to studies begun in the Jeanloz laboratory. A prominent example is the fact that glycolipids may be antigens and glycolipids of tumors may elicit an immune response in the cancer host. Another example is his research on the carbohydrate portion of glycoproteins, which was initiated in 1955, with special attention to 
1-acid glycoprotein of human serum, otherwise known as orosomucoid. This work, together with similar investigations of Robert G. Spiro, led to the unequivocal demonstration of N-acetyllactosamine in well-defined glycoproteins, such as 1-acid glycoprotein and fetuin. In this work, glycosidases (other than sialidase) were used for the first time for structura1 analysis of glycoproteins. With much foresight, Jeanloz suggested the sequence and linkage of some of the monosaccharides of what is known today as a complex biantennary oligosaccharide. Importantly, he proposed that the inside core, linked to the protein, was composed of two N-acetyl-D-glucosamine residues and several D-mannose residues. The proof of the proposed structures was, as usual, sought by Jeanloz using chemical synthesis. In 1970, he synthesized the asparagine-linked core structure GlcNAcβ1,4GlcNAcβNAsn and subsequently a large number of O- and N-linked glycopeptides.
Soon after the discovery of the dolichyl sugar phosphate intermediates involved in protein glycosylation, Jeanloz undertook the chemical synthesis of these still poorly characterized molecules. The work from his laboratory on the synthesis of dolichyl mannosyl phosphate and N-acetylglucosaminyl dolichyl phosphate and pyrophosphate is a classical example of unequivocal chemical synthesis leading the way in the establishment of new metabolic pathways. The anomeric configuration of the active compounds was determined, as was the dual role of phosphate diester and pyrophosphate derivatives in the overall pathway. At this time in the 1980s the synthetic chemistry in the Jeanloz laboratory went hand in hand with biochemistry in revealing the mode of assembly of the asparagines-linked carbohydrates.
In the late 1980s Jeanloz became interested in -mannosidosis. With his co-workers, particularly Christopher D. Warren, he identified the oligomannosides that accumulate in tissues and body fluids of cats and cows suffering from this genetic disease and characterized the substrate specificities of lysosomal -mannosidases that normally degrade these oligosaccharides. He also investigated the urinary oligosaccharides excreted by sheep with swainsonine toxicosis, the principal symptoms of which are similar to those of -mannosidosis, and established the structure of many of them mainly by his favorite methylation analysis technique.
|
Editor, symposia organizer, and experton carbohydrate nomenclature |
|---|
|
TopFrom glycogen and deoxy...Applications of methylation...Rare amino sugars, glycolipids,...Editor, symposia organizer, and...Dedicated teacher, avid... |
|---|
The productivity of Jeanloz is exemplified by his bibliography of more than 400 publications. He has authored many reviews, which are outstanding for their clarity, concise style, and interpretation. He has also edited several books, the most notable of which is The Amino Sugars, a three-volume treatise (1965–1969), co-edited with E. A. Balazs. He was particularly concerned with the nomenclature of carbohydrates and has been instrumental in resolving key issues and introducing many new and well-defined terms such as glycosaminoglycan. In addition to his research and teaching activities at Harvard and elsewhere throughout the world, Jeanloz served on numerous committees and editorial boards; among others, he was one of the founders in the early 1960s of the journal Carbohydrate Research, the first of its kind devoted to the subject.
The community of carbohydrate scientists is greatly indebted to him as a central figure in the organization of the International Symposia on Glycoconjugates. The first of these symposia was convened in 1965 in Swampscott with Jeanloz as Co-chairman. He was also the prime mover in encouraging his European colleagues to organize the second and third meetings in Lille in 1973 and in Brighton in 1975, respectively, and was active in the organization of the 4th Symposium on Glycoconjugates held at Wood's Hole. Together with John Gregory he edited the two-volume proceedings of this symposium. During 1974–1975, Jeanloz was President of the National Society of Complex Carbohydrates. He has also been active for many years in the Division of Carbohydrate Chemistry of the American Chemical Society and served as its Chairman. His numerous achievements have brought him many national and international honors. These include the Medal of the Societe de Chimie Biologique de France; Medal of the University de Liege; Prix Jaubert, University of Geneva; Claude S. Hudson Award, American Chemical Society; Docteur Honoris Causa, University of Paris; and recently the Alexander von Humboldt Award, Germany's most prestigious scientific award.
|
Dedicated teacher, avid sportsman, and inveterate traveler |
|---|
|
TopFrom glycogen and deoxy...Applications of methylation...Rare amino sugars, glycolipids,...Editor, symposia organizer, and...Dedicated teacher, avid... |
|---|
The scope of Jeanloz's activities and the knowledge and enthusiasm that he imparted to his colleagues all combined to inspire his many students. He was for many years a tutor with the Faculty of Arts and Sciences of Harvard University, retiring from this activity only a few months before his death. Because of his qualities, he was able to attract and keep many able associates in his laboratory for long periods and frequently to continue collaborations with them after they left. The excellent training they received from Jeanloz and the contacts and friendships made in his laboratory exercised decisive influence on their careers. His demonstration of the importance of applying the rigorous techniques of organic chemistry to the solution of biochemical problems is the most crucial point of this training.
The uniquely congenial atmosphere in the Jeanloz laboratory that is remembered with affection by those who worked with him has been aided greatly by the presence of his charming wife, Dorothea, an organic chemist, who has collaborated with him for many years. In spite of their busy schedules, Dorothea and Roger always took great interest in the well-being of their associates. Jeanloz's personal qualities and bon vivant character endeared him to all of his colleagues.
Jeanloz was an inveterate traveler, who taught students from about as many countries as he had visited, a total difficult to tally in any category. In his younger years he was a skilled alpinist and made many of the classical climbs in the Swiss-French Alps. He was also an expert skier, a sport he continued to enjoy into his more advanced years,often accompanied by his grandchildren. Jeanloz was a lover of classical music and an enthusiastic gardener. His love for plants came early in his life when he brought bouquets of alpine flowers from mountain expeditions. His interest in sports can be traced to his childhood. At the age of 12 he started playing basketball that had been introduced into Switzerland by the American YMCA. He was a member of the Geneva team that was selected to represent Switzerland in international games. Later he became a keen tennis player and was a familiar figure on the tennis courts of the MGH and in the Longwood Cricket Club near the family home.
In 1986, a symposium was held to honor Roger Jeanloz as part of the 8th International Symposium on Glycoconjugates in Houston, TX. For this occasion the eminent British scientist Albert Neuberger wrote: "His work is characterized by a mastery of all chemical and biological methods used; by reliability of the results obtained; and by careful and balanced interpretation. There is hardly any topic in this wide field which he has not touched and which has not benefited from his research ... Roger Jeanloz has made his laboratory one of the few outstanding centers in the field of complex carbohydrates. His combination of supreme chemical competence and biological understanding are the hallmark of his career."
Roger Jeanloz will be remembered with love and utmost respect by his many friends, colleagues, and disciples worldwide.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||