Some questions are discussed. Can an organism live without any glycosphingolipids(GSLs)? If it can, how? What tests are needed to prove that an organism contains little or no GSLs? Does lack of reaction with antibodies prove that the lipid is absent? Does lack of incorporation of labeled precursors show that the lipid substrates are really absent? Are most of the GSLs in a cell unnecessary for normal, minimal functioning? Perhaps these questions will encourage glycobiology researchers to investigate some new approaches.

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Irrespective of whether the track to a cell surface molecule takes its start from a function in search for the molecule or from a molecule in search for its function, the definite elucidation of the mechanistic basis frequently requires cloning and sequencing of the genetic information. Upon further characterization it may then turn out that the sequence in question is associated with additional, unexpected functions. This sometimes leads to idiosyncratic conclusions which may or may not prove to be misleading, especially when it becomes obvious that what initially appeared as a single sequence or molecule is in reality a family of molecules that is generated by alternative splicing. The sequence of events relating to the elucidation of structure/function relationships of the CD44 surface molecule(s) followed exactly this track. Interest was stipulated quite independently by research in the areas of lymphocyte homing and extracellular matrix anchorage, the common denominator possibly being the binding to hyaluronic acid(HA). At the moment we are in a phase of deciphering molecular diversity in the CD44 family of cell surface receptors, the most urgent task being the assignment of individual functions to the rapidly growing number of family members.

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Recent studies on therapeutic proteins including tissue-type plasminogen activator, erythropoietin, and granulocyte-macrophage colony stimulating factor revealed that oligosaccharides attached to them had crucial roles in a variety of biological and physical properties. Our studies on granulocyte colony stimulating factor and prourokinase showed that the designed addition of N-linked oligosaccharide chains on them improved in vitro and in vivo biological properties such as protease susceptibility, thermal stability, and prolongation of in vivo half life.

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Integrins are a family of cell surface, transmembrane, heterodimeric glycoprotein complexes consisting of an α and a β subunit that act as cell-substrate and cell-cell adhesion receptors. The β₁-containing integrins are the major cell adhesion receptors on many cell types for such extracellular matrix and basement membrane components as collagen, laminin, and fibronectin. Intracellular maturation of the asparagine-linked carbohydrates on β₁ integrins is unusually slow, involves the addition of are latively large glycan structure, and is required for the acquisition of ligand-binding activity of the α₅β₁ high affinity fibronectin-binding integrin. Ligand-binding function may be specifically associated with sialylation of the β₁ integrin. Activation of keratinocytes, which is accompanied by increased adhesiveness to, and migration on, fibronectin substrates, is also associated with changes in the intracellular glycan processing of integrins. Oncogenic transformation does not necessarily result in changes in the cell surface expression of β₁ integrins but does increase the rate of integrin processing, decrease the size of the intracellular pool of immature integrin β₁ polypeptides, and alter the cell-surface localization of integrins.

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The general features and the different method for the synthesis of TMSEt glycosides are discussed. TMSEt glycosides of mono-hexasaccharides were transformed into the corresponding hemiacetals (39 compound; average yield: 92%), 1-O-acyl sugars with conserved anomeric configuration (34 compounds; average yield; 97%), and 1-chloro sugars (16 compounds; average yield: 96%).

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