Glycosylation can have a major impact on biosynthesis and bioactivity of glycoproteins. The specific functions of asparagine-linked (N-linked) and serine- or threonine-linked (O-linked) oligosaccharides have been defined in some cases, and implied in others. This review discusses some examples of the diversity of functions that have been ascribed to N- and O-linked oligosaccharides.
It has become evident that a recently defined sphingomyelin metabolic pathway can function in signal transduction. Ceramide, generated by sphingomyelin hydrolysis, plays a role as second messenger and stimulates a membrane-bound serine/threonine kinase termed ceramide-activated protein kinase. This pathway appears to mediate signal transduction for tumor necrosis factor-α. It is presumed that other cell-surface receptors may utilize this pathway for signalling.
Syndecans are family of four cell surface proteoglycans with conserved plasma membrane and cytoplasmic domains. The ectodomains contain convalently linked glycosaminogly can chains which mainly consist of heparan sulfate (HS) but also of chondroitin sulfate (CS). The prototype of syndecan family, syndecan-I, has been shown to bind selectively several extracellular matrix molecules via its HS chains. It can simultaneously bind also heparin binding growth factors and predict the site of growth promotion by immoblizing the tyrosine kinase receptor complex to site of syndecan-matrix interaction. Besides growth promotion syndecan also participates in the regulation of cell morphology by supporting the organization of cytoskeletal elements of epithelial cells. This type of regulation could be important for normal maintenance of epithelial morphology because syndecan expression has been shown to decline or to be lost in several transformed epithelial cell. Binding of two types of extracellular effector molecules by HS chains has provided for syndecan an unique way to participate in the regulation of cell growth and morphology, and indicates the importance of carbohydrate studies in cell biology.
An overview is given on the use of 2-oxo- and 2-oximinoglycosyl bromides for the practical acquisition of β-D-mannose and β-D-mannosamine-containing oligosaccharides of biological importance: any mono- or di-saccharide can easily be converted by known methodology into its 2-hydroxyglycal ester; these, by simple treatment with NBS/methanol, afford the respective glycosulosyl bromides in high yield; alternately, they may be converted into oximinoglycosyl bromides in a three-step sequence comprising hydroxylaminolysis, benzoylation, and photobromination as to allow overall yields of around 50%. Due to a non-participating, strongly electron-withdrawing substituent next to the anomeric center, β-glycosidation is essentially stereospecific. The subsequent hydride reduction of the oxo and oximino functions is equally endowed with high, in most cases exclusive stereoselectivity for attack of the hydride ion from the α-face, i.e. opposite to the anomeric substituent, thus leading to β-D-manno-configurated hexose and hexosamine units. The present state of exploitation of this methodology for the straightforward synthesis of oligosaccharides with β-D-mannose and N-acetyl-β-D-mannosamine units is highlighted.
The 21st Annual Meeting of the Society of Complex Carbohydrates, organized by Carl Hellerqvist, Vanderbilt Univ. Sch. of Med., was held in Nashville, TN, Nov. 11-14, 1992. The meeting was divided into eight scientific sessions, using a format patterned after the International Glycoconjugate meeting in Toronto, 1991. To the delight of many participants, there were no concurrent sessions. Regrettably, there was no provision for coffee break between sessions and there was no allocation of specific poster viewing time. There were over 350 participants, including many young “glyco-scientists” who were aided by the 22 travel fellowships of $300 each issued by the Society to help students and postdoctorals attend the meeting. This is an excellent policy which should be maintained. The abstracts of this meeting were printed by Oxford University Press as a part of the October, 1992, issue of Glycobiology.