title: Synthesis of β(1,3) oligoglucans exhibiting a Dectin-1 binding affinity and their biological evaluation.
abstract: In this report, we describe the synthesis and biological evaluation of β(1,3) oligosaccharides that contain an aminoalkyl group and their biological evaluation. A 2,3 diol glycoside with a 4,6 benzylidene protecting group was used as an effective glycosyl acceptor for the synthesis of some β(1,3) linked glycosides. The use of a combination of a linear tetrasaccharide and a branched pentasaccharide as glycosyl donors led to the preparation of β(1,3) linear octa- to hexadecasaccharides and branched nona- to heptadecasaccharides in good total yields. Measurements of the competitive effects of the oligosaccharides on the binding of a soluble form of Dectin-1 to a solid-supported Schizophyllan (SPG) revealed that the branched heptadecasaccharide and the linear hexadecasaccharides also have binding activity for Dectin-1. In addition, the two oligosaccharides, both of which contain a β(1,3) hexadecasaccharide backbone, exhibited agonist activity in a luciferase-assisted NF-κB assay. STD-NMR analyses of complexes of Dectin-1 and the linear hexadecasaccharides clearly indicate Dectin-1 specifically recognizes the sugar part of the oligosaccharides and not the aminoalkyl chain.
authors.affiliation: Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1-S1-35 Ookayama, Meguro, Tokyo 152-8552, Japan. thiroshi@apc.titech.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Adachi
authors.forename: Shinya
authors.initials: S
authors.lastname: Hanashima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Naohito
authors.initials: N
authors.lastname: Ohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000819:agonists / Q000378:metabolism; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012567:Schizophyllum / Q000737:chemistry; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008156:Luciferases; D016328:NF-kappa B; D009844:Oligosaccharides; D000099181:Dectin-1