45 硫酸化天然多糖ヘパリンと血小板との相互作用に関する研究(口頭発表の部)

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Heparin, a structurally heterogeneous and highly sulfated polysaccharide, is widely used in clinical treatments as an anticoagulant. Pharmaceutical heparin, however, is known to bind to human platelets, and may directly alter platelet function and induce immuno-sensitization. Toward the goals of developing heparins with safer therapeutic effects and developing a clearer understanding of the interaction between heparin and platelets at the molecular level, we examined the structural specificity of heparin's binding to platelets and heparin-binding proteins on the surface of platelets. In this paper, we will discuss: ・The effective fluorescent and ^<125>-iodine labelling of heparin with a newly developed labeling reagent was established. The labelled heparin contained nearly normal biological activity. ・Several heparin binding proteins in the membrane fraction of platelet were identified by the gel-overlay procedure (References and note [7]), as well as ligand-blotting method using ^<125>I-labelled heparin. The proteins were evaluated by the modified gel-overly procedure and a immuno-staining technique in order to isolate heparin binding proteins which act as heparin receptors. ・By binding competition study, the disaccharide unit (2-deoxy-2-sulfoamide-6-O-sulfo-α-D-glycopyranosyl)-(1→4)-O-(2-O-sulfo-α-L-idopyranosyluronic acid), designated as NS6S-I2S, in heparin molecule was predicted to be a key disaccharide unit for the binding of heparin to platelets. The prediction was subsequently confirmed by the synthetic approach of preparing the disaccharide unit containing NS6S-I2S. Also, the clustering effect depending on NS6S-I2S was shown by using heparin derived oligosaccharides and is currently being evaluated with a synthetic compound containing 2 units of NS6S-I2S. The platelet-binding sequence in heparin, including NS6S-I2S, was further analyzed using heparin derived tetrasaccharides.
天然有機化合物討論会の論文
1995-09-01

45 硫酸化天然多糖ヘパリンと血小板との相互作用に関する研究(口頭発表の部)

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