High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery

Yasuhiko Kizuka, Sho Funayama, Hidehiko Shogomori, Miyako Nakano, Kazuki Nakajima, Ritsuko Oka, Shinobu Kitazume, Yoshiki Yamaguchi, Masahiro Sano, Hiroaki Korekane, Tsui Ling Hsu, Hsiu Yu Lee, Chi Huey Wong, Naoyuki Taniguchi

研究成果: Article

10 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)782-792
ページ数11
ジャーナルCell Chemical Biology
23
発行部数7
DOI
出版物ステータスPublished - 21-07-2016

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Fucose
Biomarkers
Polysaccharides
Toxicity
Imaging techniques
Sugars
Labeling
Glycomics
Fucosyltransferases
Physiological Phenomena
Glycoconjugates
Guanosine
Diphosphates
Fibroblasts
Cytotoxicity
Mass spectrometry
Mass Spectrometry
Glycoproteins
Derivatives

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

これを引用

Kizuka, Yasuhiko ; Funayama, Sho ; Shogomori, Hidehiko ; Nakano, Miyako ; Nakajima, Kazuki ; Oka, Ritsuko ; Kitazume, Shinobu ; Yamaguchi, Yoshiki ; Sano, Masahiro ; Korekane, Hiroaki ; Hsu, Tsui Ling ; Lee, Hsiu Yu ; Wong, Chi Huey ; Taniguchi, Naoyuki. / High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery. :: Cell Chemical Biology. 2016 ; 巻 23, 番号 7. pp. 782-792.
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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.",
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Kizuka, Y, Funayama, S, Shogomori, H, Nakano, M, Nakajima, K, Oka, R, Kitazume, S, Yamaguchi, Y, Sano, M, Korekane, H, Hsu, TL, Lee, HY, Wong, CH & Taniguchi, N 2016, 'High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery', Cell Chemical Biology, 巻. 23, 番号 7, pp. 782-792. https://doi.org/10.1016/j.chembiol.2016.06.010

High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery. / Kizuka, Yasuhiko; Funayama, Sho; Shogomori, Hidehiko; Nakano, Miyako; Nakajima, Kazuki; Oka, Ritsuko; Kitazume, Shinobu; Yamaguchi, Yoshiki; Sano, Masahiro; Korekane, Hiroaki; Hsu, Tsui Ling; Lee, Hsiu Yu; Wong, Chi Huey; Taniguchi, Naoyuki.

:: Cell Chemical Biology, 巻 23, 番号 7, 21.07.2016, p. 782-792.

研究成果: Article

TY - JOUR

T1 - High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery

AU - Kizuka, Yasuhiko

AU - Funayama, Sho

AU - Shogomori, Hidehiko

AU - Nakano, Miyako

AU - Nakajima, Kazuki

AU - Oka, Ritsuko

AU - Kitazume, Shinobu

AU - Yamaguchi, Yoshiki

AU - Sano, Masahiro

AU - Korekane, Hiroaki

AU - Hsu, Tsui Ling

AU - Lee, Hsiu Yu

AU - Wong, Chi Huey

AU - Taniguchi, Naoyuki

PY - 2016/7/21

Y1 - 2016/7/21

N2 - 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.

AB - 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.

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