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.
| Original language | English |
|---|---|
| Pages (from-to) | 782-792 |
| Number of pages | 11 |
| Journal | Cell Chemical Biology |
| Volume | 23 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 21-07-2016 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry
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}
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.
In: Cell Chemical Biology, Vol. 23, No. 7, 21.07.2016, p. 782-792.Research output: Contribution to journal › 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.
UR - http://www.scopus.com/inward/record.url?scp=84978766433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978766433&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2016.06.010
DO - 10.1016/j.chembiol.2016.06.010
M3 - Article
C2 - 27447047
AN - SCOPUS:84978766433
VL - 23
SP - 782
EP - 792
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 7
ER -