Synthesis Of CVF Oligosaccharide Fragments And Their Analogues

Cobra venom factor (CVF) is a nontoxic glycoprotein present in cobra venom with strong complement-activating activity through the alternative pathway. When conjugated to monoclonal antibody or its fragment F(ab)₂' CVF generates cytotoxicity selectively killing the cells of melanoma, leukemia, and neuroblastoma. The structure of the oligosaccharide in the chains of α and β of CVF was determined in 1991 with very little knowledge for its functions and biological activities. Since the oligosaccharide contains Le^x antigen, a well-known tumor-associated carbohydrate antigen, we suggested that the oligosaccharide component of CVF might have tumor immunogenicity, and thus selected from the nonreducing end of the whole CVF oligsaccharide molecule a tetrasaccharide fragment, Galα(1-3)Galβ(1-4)[Fuca(l-3)]GlcNAc, which contains the Le^x antigen, as our target compound. It was anticipated to have tumor immunogenic activity, so the study on it might contribute to the development of immunotherapy of tumors.Because cluster structures show increased antigenicity and in addition, in natural glycoproteins the antenary oligosaccharide side chains enable a multiple presentation of the saccharide determinants, our aim was the synthesis of the target tetrasaccharide with a azido-containing spacer arm, which can be easily reduced to an amino group to conjugate with protein in order to mimic the multiantenary Le^x antigen structures.