title: High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery.
abstract: Fucose, a terminal sugar in glycoconjugates, critically regulates various physiological and pathological phenomena, including cancer development and inflammation. However, there are currently no probes for efficient labeling and detection of this sugar. We chemically synthesized a novel series of alkynyl-fucose analogs as probe candidates and found that 7-alkynyl-fucose gave the highest labeling efficiency and low cytotoxicity. Among the fucose analogs, 7-alkynyl-fucose was the best substrate against all five fucosyltransferases examined. We confirmed its conversion to the corresponding guanosine diphosphate derivative in cells and found that cellular glycoproteins were labeled much more efficiently with 7-alkynyl-fucose than with an existing probe. 7-Alkynyl-fucose was detected in the N-glycan core by mass spectrometry, and 7-alkynyl-fucose-modified proteins mostly disappeared in core-fucose-deficient mouse embryonic fibroblasts, suggesting that this analog mainly labeled core fucose in these cells. These results indicate that 7-alkynyl-fucose is a highly sensitive and powerful tool for basic glycobiology research and clinical application for biomarker discovery.
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Funayama
authors.affiliation: Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Shogomori
authors.affiliation: Graduate School of Advanced Sciences of Matter, Hiroshima University, Hiroshima 739-8530, Japan.
authors.forename: Miyako
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan; Molecular Membrane Neuroscience, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oka
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: Structural Glycobiology Team, Global Research Cluster, RIKEN, Saitama 351-0198, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sano
authors.affiliation: Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Korekane
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hsiu-Yu
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.affiliation: Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Department of Disease Glycomics (Seikagaku Corporation), Research Institute for Microbial Diseases, Osaka University, Osaka 567-0047, Japan. Electronic address: dglycotani@riken.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005643:Fucose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011134:Polysaccharides / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D015335:Molecular Probes; D011134:Polysaccharides; D005643:Fucose