Carbohydrates, sometimes in the form of oligosaccharides, are deeply involved in a wide range of biological phenomena including metabolism, intercellular recognition, and infection, etc. Adding the fact that the expression of some glycosyltransferase is directly related to metastasis, it is important to pursue a research into the recognition mechanism between carbohydrates and proteins, which may lead to the discovery of new therapeutic treatment. However, our current knowledge regarding these bindings limits designing and creating potent inhibitors of such interactions. Combinatorial chemistry, therefore, is considered very useful and important in discovering what we are looking for. Another aspect of carbohydrates is that they consist of continuous chiral centers, which can be utilized as a scaffold. This review attempts to summarize the current growth area of carbohydrate based library synthesis. Research, which describes ideas aiming at a carbohydrate library and is very important in the future, had to be omitted.
Rapid in vitro screening from various molecular libraries has come of age as a molecular recognition technology, which we refer to as “Biocombinatorial Chemistry”. Phage-displayed library, a biocombinatorial chemistry tool, is a representative method based on the affinity binding between the displayed library and target molecule or tissue. Biopanning with the phage-displayed peptide library has been used to determine the epitope of the target antigen protein. We introduced this method to create peptides, which mimic carbohydrate structure using a monoclonal antibody against the carbohydrate moiety of the glycoconjugate. The peptide obtained by this procedure could mimic the function of the carbohydrate. Based on our observations, we proposed to call those peptides “Glyco-Replica Peptides”. In this review, preparation of the peptides and functional roles of the obtained peptides are described.
A nematode Caenorhabditis elegans has been used as a model organism for the study of animal development and neurons. Recently, essentially complete DNA sequence of the genome was determined and published [Science (1998), 282, 2011-2045]. C. elegans has become of interest in studying the genes whose biological functions are unknown to biologists who are not studying C. elegans, because not only classic genetics but also reverse genetics such as gene knockout can be used in C. elegans. In this manuscript I will briefly explain the methods of searching for the C. elegans homologue of your interested genes using the Internet. How to use DDBJ has already been described [TIGG (1999), 11, 119-127]. Here I write about the homepages of Washington University Genome Sequencing Center, The Sanger Center and ACeDB.
Heparin and heparan sulphate (HS) are sulphated polysaccharides of the glycosaminoglycan (GAG) type and parts of proteoglycan (PG) macromolecules. HSs are located at most cell surfaces and in the extracellular matrix, where they bind to various proteins, thereby affecting biological processes. In my thesis two proteins involved in HS metabolism have been studied. One is a mammalian heparanase, which degrades HS, the other is the N-deacetylase/N-sulphotransferase (NDST), taking part in generation of the complex structure of HS. Heparanases cleave HS only at a few sites, generating HS fragments. Studies on the physiological functions of this partial degradation suggest involvement in biologically important processes such as tumour metastasis, angiogenesis, regulation of cell growth, lipid metabolism and blood coagulation. Heparanases recognise a particular structure in the HS chain, which is characterised in this thesis (1). A novel approach, based on systematic modification of a bacterial polysaccharide was used to generate different model substrates. HS chains contain several structural elements that are important in binding to different proteins. The generation of such specific structures requires a number of enzymes. NDST determines in what regions of the polysaccharide chain sulphation will occur. Characterisation of this enzyme is the other main topic of this thesis (2-5). In particular, the goal was to elucidate the effect of different NDST isoforms on HS structure.