Claude S. Hudson Award in Carbohydrate Chemistry

Sponsored by National Starch & Chemical

For nearly four decades, Johns Hopkins University professor YUAN CHUAN LEE has devoted himself to glycobiology and glycosciences. His persistent efforts have enabled significant advances in the understanding of glycoconjugates such as glycoproteins and glycolipids.

A professor since 1974, Lee started teaching and researching at Johns Hopkins in 1965. One colleague who started collaborating with Lee in 1967 recalls: "At that time, we knew there were glycoproteins, glycolipids, and other complex glycoconjugates and that cell surfaces were covered by a very poorly described 'glycocalyx.' Furthermore, there was the intuitive feeling that perhaps these complex sugars might be involved in intercellular communications. But the problems facing us were enormous, perhaps insoluble."

Lee's research yielded many insights. For instance, he found ways to analyze both qualitatively and quantitatively the composition of glycoconjugates and also to determine their structure. Along the way, Lee developed one of the first automated sugar analyzers, which consisted of a cation-exchange column for amino sugars and an anion column for neutral sugars in the 10-nmol range. These inventions eventually evolved to the form of HPAEC (high-performance anion-exchange chromatography), which is faster and more sensitive (about 0.1-nmol range). HPAEC is now a standard instrumentation in most carbohydrate research laboratories.

Using such analytical tools, Lee established the structures of many N- and O-linked glycans. He was the first to put forth the concept of "core structure" for the N-glycoside, notes an academic familiar with Lee's work.

Providing more precise tools to investigate recognition of carbohydrates, Lee devised "neoglycoproteins" (a term coined by Lee), which are proteins modified with carbohydrate derivatives having definitive structures. Later on, the term neoglycoconjugate was introduced to include other structures such as neoglycolipids and neoglycopolymers. "Many of the advances in the field of glycobiology have been made possible by the availability of neoglycoconjugates, and Lee has been a pioneer in the development of methods for their synthesis," notes a professor of chemistry and biochemistry familiar with Lee's achievements. Another researcher believes that the development of neoglycoproteins "has had the most immediate and forceful impact upon the field of glycobiology."

One of his more important contributions, Lee comments, was his work on the importance of multivalency in carbohydrate recognition. Initially published in 1983 in the Journal of Biological Chemistry, the study found that there are tremendous affinity enhancements in the binding of galactose or N-acetylgalactosamine with mammalian hepatic receptor (C&EN, Oct. 9, 2000, page 49). Divalent and trivalent glycosides were bound roughly 1,000 and 1 million times stronger than the monovalent glycosides. This was referred to as "glycoside clustering effect."

Lee's associates note his ability to combine the tools of biology and chemistry. "Many of Lee's advances have been made possible because of his expertise in synthetic carbohydrate chemistry and by his ability to devise new synthetic strategies," one says. "For instance, he synthesized the dimer, trimer, and tetramer analogs of chitooligosaccharides in which the glycosidic oxygen atoms were replaced with sulfur atoms and demonstrated, in studies performed in collaboration with Saul Roseman, that they were extremely useful in deciphering operation of the chitinase system bacteria."

Born in Taiwan, Lee earned in 1957 a master's degree in agricultural chemistry from National Taiwan University in Taipei. He obtained in 1962 a doctorate degree in biochemistry from the University of Iowa. His graduate thesis, supervised by Rex Montgomery, was on the subject of carbohydrate structure of chicken ovalbumin. This thesis, as well as postgraduate work at the University of California, Berkeley, with Clinton Ballou on the subject of Mycobacterium glycolipids and lipopolysaccharides, motivated Lee to devote himself to the study of glycobiology and glycosciences.

Lee's considerable impact as a re-searcher is evident from his authorship of nearly 300 academic papers. Moreover, Lee is the coauthor of seven patents, some of which were licensed to companies in Japan.

Having achieved a considerable stature in the U.S. research community, Lee shared his expertise with various academic communities in East Asia. Since the 1980s, Lee, who is fluent both in Chinese and Japanese, has been a visiting scholar at universities in Kyoto, Taipei, Beijing, and Shanghai. He also sits on the advisory board of several scientific institutes in Japan and Taiwan.

Academics who study glycobiology describe Lee as a giant, notes a researcher familiar with Lee's work. "One can say without hesitation that the work of Lee has been the driving force in influencing the course and development of glycobiology during the latter quarter of the 20th century."

The award address will be presented before the Division of Carbohydrate Chemistry.

JEAN-FRANCOIS TREMBLAY

(From Chem. & Eng. News, Jan. 15, 2001)