title: Chemical Synthesis and Evaluation of a Disialic Acid-Containing Dextran Polymer as an Inhibitor for the Interaction between Siglec 7 and Its Ligand.
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 KDvalue of 5.87×10-10m, and a high inhibitory activity for the interaction between Siglec7 and a ligand (GD3), with a IC50value 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.
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H-101, Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Airi
authors.initials: A
authors.lastname: Mori
authors.affiliation: Department of Chemical Science and Engineering, Tokyo Institute of Technology, 2-12-1-H-101, Ookayama, Meguro, Tokyo, 152-8552, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Yokohama University of Pharmacy, 601, Matano-chou, Totsuka-ku, Yokohama, Kanagawa, 245-0066, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kitajima
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sato
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D060326:Chemistry Techniques, Synthetic; D003412:Cricetulus; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D037102:Lectins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D003911:Dextrans; D005456:Fluorescent Dyes; D005732:Gangliosides; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D037102:Lectins; D008024:Ligands; D011993:Recombinant Fusion Proteins; C402206:SIGLEC7 protein, human; D012794:Sialic Acids; C026226:ganglioside, GD3
keywords: NK cells; Siglec; glycopolymers; inhibitors; sialic acid