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  • Title: Chemical Synthesis and Evaluation of a Disialic Acid-Containing Dextran Polymer as an Inhibitor for the Interaction between Siglec 7 and Its Ligand.
    Author: Yamaguchi S, Yoshimura A, Yasuda Y, Mori A, Tanaka H, Takahashi T, Kitajima K, Sato C.
    Journal: Chembiochem; 2017 Jul 04; 18(13):1194-1203. PubMed ID: 28374980.
    Abstract:
    A new sialic acid (Sia)-containing glycopolymer-a fluorescent probe with high-density disialic acid (diSia) on the surface of polysaccharide dextran (diSia-Dex)-was synthesized as a key molecule to regulate the Sia recognition lectins, Siglecs, that are involved in the immune system. According to our original methods, diSia was synthesized by α-selective sialylation, and a dextran template possessing terminal acetylenes and amino groups was prepared. A diSia and a fluorescent molecule were subsequently introduced to surface-modified dextran by Hüisgen reaction and amidation, respectively. The modulatory activity of Siglec7 was evaluated by using synthetic probes. DiSia-Dex showed high binding avidity toward Siglec7, with a KD value of 5.87×10-10  m, and a high inhibitory activity for the interaction between Siglec7 and a ligand (GD3), with a IC50 value of 1.0 nm. Notably, diSia-Dex was able to release Siglec7 from the pre-existing Siglec7-GD3 complex, possibly due to its unique properties of a slow dissociation rate and a high association rate. Together, these data show that diSia-Dex can be widely applicable as a modulator of Siglec7 functions.
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