Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine, N,N′-diacetylchitobiose and N-acetyllactosamine: Analysis of cross-linking activities with WGA and ECA lectins

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• 作者：Ryuichi Masaka ; Makoto Ogata ; Yoshinori Misawa ; Megumi Yano ; Chika Hashimoto ; Takeomi Murata ; Hirokazu Kawagishi ; Taichi Usui
• 关键词：Tetravalent glycoside ; Molecular design ; Glycomimetics ; Multivalency effect ; WGA/ECA lectin
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 January 2010
• 年：2010
• 卷：18
• 期：2
• 页码：621-629
• 全文大小：601 K

文摘

Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N′-diacetylchitobiose [(GlcNAc)₂] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cristagalli) agglutinin (ECA) with a series of tetravalent glycosides and related compounds were studied using a hemagglutination inhibition assay, a precipitation assay, double-diffusion test, and an optical biosensor based on surface plasmon resonance (SPR). The tetravalent glycosides were found to be capable of binding and precipitating the lectins as tetravalent ligands. Strong interactions with WGA, due to a combination of multivalency effects and spacer effects, were observed for tetravalent glycosides bearing flexible tandem GlcNAc. The chelate effect leads to large rate enhancement for the tetravalent system with favorable orientation of ligands. Our simple strategy produced multivalent glycosides with strong cross-linking activity for lectin as a specific coagulant.