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.
Keywords:
NK cells; Siglec; glycopolymers; inhibitors; sialic acid.
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, Myelomonocytic / chemistry*
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Antigens, Differentiation, Myelomonocytic / genetics
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Antigens, Differentiation, Myelomonocytic / metabolism
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Binding Sites
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CHO Cells
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Carbohydrate Conformation
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Carbohydrate Sequence
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Chemistry Techniques, Synthetic
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Cricetulus
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Dextrans / chemical synthesis
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Dextrans / chemistry*
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Dextrans / metabolism
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Dextrans / pharmacology
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Fluorescent Dyes / chemistry
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Gangliosides / antagonists & inhibitors
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Gangliosides / chemistry*
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Gangliosides / metabolism
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Gene Expression
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Humans
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Immunoglobulin Fc Fragments / chemistry
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / metabolism
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Immunoglobulin G / chemistry
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Immunoglobulin G / genetics
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Immunoglobulin G / metabolism
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Kinetics
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Lectins / antagonists & inhibitors
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Lectins / chemistry*
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Lectins / genetics
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Lectins / metabolism
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Ligands
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Molecular Docking Simulation
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Protein Binding / drug effects
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Recombinant Fusion Proteins / chemistry*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sialic Acids / chemistry*
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Sialic Acids / metabolism
Substances
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Antigens, Differentiation, Myelomonocytic
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Dextrans
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Fluorescent Dyes
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Gangliosides
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Lectins
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Ligands
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Recombinant Fusion Proteins
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SIGLEC7 protein, human
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Sialic Acids
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ganglioside, GD3