Molecular conformations in proteoglycan aggregation.

that murein will eventually be discovered to require an apoprotein as the initiator, as is turning out to be the case with a number of, what were for long thought to be, ‘pure’ polysaccharides. Examples are the proteoglycans of connective tissue, and storage polysaccharides such as glycogen. No less exciting have been the developments in understanding the stereochemistry of the proteoglycans, the ‘grund Substanz’ of connective tissue. It is not many years since Helen Muir showed that in some way the ‘mucopolysaccharide’ of nasal septa was linked covalently to serine residues of a protein backbone. Her work was the basis for the later understanding, as a result of the studies of Lennart Rodin in Chicago and of Karl Meyer ,in New York, in the early 1960’s, of why relatively mild alkaline conditions resulted in the loss of viscosity of proteoglycan solutions. The results of a number of physicochemical studies are beginning to yield an insight into the manner in which the specific organization of proteoglycans within connective tissue is necessary-involving a highly specific interaction of hyaluronic acid with ordered binding sites on a region of the protein backbone of the proteoglycan-as a pre-requisite for the organization of water molecules within the tissue, needed to give rise to firmness without rigidity. The high incidence of rheumatoid arthritis is perhaps among the main reasons why so much attention has been devoted to the ground substance of connective tissues, but the understanding, as a result of these studies, of the underlying chemistry of such rare, but devastating, inborn metabolic defects as Hurler’s, Hunter’s, San Fillip0 and Morquio syndromes has added further stimulus to the work. A more extensive stereochemical approach to these latter areas could yield important clues to more effective treatment of the conditions. Perhaps the greatest stimulus to the study of glycoconjugates has come about as a result of the realization that the specific types of sugar residues within a carbohydrate moiety can act as specific recognition signals. Once again, this area developed from the examination of a biological problem with its roots in pathology, namely, the interaction of the influenza virus with cells of the body. The problem, initiated by G. K. Hirst in 1942, was the mechanism by means of which the virus can cause agglutination of isolated red cells, and it was pursued by Sir MacFarlane Burnet and more fully, by Alfred Gottschalk in Melbourne in the early 1950’s. Gottschalk’ work resulted in the eventual elucidation of the structure of the sugar residue on the red cell to which the virus initially attached itself, namely sialic acid. Of equal importance was the realization that there was a lectin, with specificity for sialic acid residues, as part of the structure of the virus. Thus was born the general idea that interactions of bacteria, fungi and viruses with plant and animal cells, of cells with one another, and of glycoproteins with cells having a specific requirement to take up these types of macromolecules, might be the result of lectin-sugar interactions. Many reasons might be given for the need to understand the stereochemistry of these types of interactions, not least of which is the likelihood that the information will be of value in solving a number of practical problems. No less important, although not dealt with at this meeting, are the stereochemical aspects of the ABO, Lewis blood group system, including the basis for the interesting cross-specificity of the B-forming enzyme with antibody raised in rabbits against purified A-forming enzyme. As long as the study of the chemistry and physics of the glycoconjugates does not become dissociated from the realization that a major purpose of work of this nature is to resolve problems of living entities, we can look forward to many exciting developments in the near future.