Discoveries of the structures of sialic acid and CMP-sialic acid (1957–1960): a letter from Saul Roseman

Abstract

Sialic acids have a special place in vertebrate glycobiology, where they constitute the dominant terminal saccharides on many cell surface glycans. From early studies that identified sialoglycans as receptors for important pathogens and toxins to more recent discoveries of sialic acid-binding proteins essential for immune system (and other) functions in humans, sialic acids and sialoglycans have become cornerstones in understanding vertebrate glycobiology and pathology. During a remarkable 3-year period in the late 1950s, a newly minted postdoctoral fellow (Donald G. Comb) and his young mentor (Saul Roseman) made a surprising series of discoveries that put sialic acid research on sound chemical and biochemical footing. A detailed personal letter written by Dr. Roseman that describes this period of intense sialic acid discovery, complete with inserted figures, was given to one of us (Y.C.L.) several years later. The text and figures of this letter provide a look back at the enthusiasm, rigor and serendipity that led to their important findings through the eyes of one of the key figures in sialic acid research.

Exploration of the Sialic Acid World

“…230 The finding of N-acetylmannosamine instead of N-acetylglucosamine also played a major role in the elucidation of the final structure of N-acetylneuraminic acid. In a detailed personal letter handed over to Yuan C. Lee, and recently published by Schnaar and Lee, 731 Roseman describes the full GlcNAc vs ManNAc story, wherein Don Comb played such a great role. With respect to the quantification of N-acetylhexosamine using the Morgan-Elson color reaction, he memorized that this assay was used for the acylneuraminate-pyruvate lyase degradation of N-acetylneuraminic acid.…”

What is the Sugar Code?

“…[25] Interestingly, this already holds true for individual letters: the elucidation of the structure of the cited N-acetylneuraminic acid, for which a total of 11 structures were proposed over time, took 25 years. [26] After having surveyed the structural basis for reading high-level versatility within the sugar code, we now move from the alphabet of sugar letters to the vocabulary of glycans.…”

“…“In this remarkable age of genomics, proteomics, and functional proteomics, I am often asked by my colleagues why glycobiology has apparently lagged so far behind the other fields. The simple answer is that glycoconjugates are much more complex, variegated, and difficult to study than proteins or nucleic acids.” [25] Interestingly, this already holds true for individual letters: the elucidation of the structure of the cited N ‐acetylneuraminic acid, for which a total of 11 structures were proposed over time, took 25 years [26] . After having surveyed the structural basis for reading high‐level versatility within the sugar code, we now move from the alphabet of sugar letters to the vocabulary of glycans.…”