High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery. Issue 7 (21st July 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cell chemical biology. Volume 23:Issue 7(2016)
• Page Start: 782
• Page End: 792
• Publication Date: 2016-07-21
• Subjects: Biochemistry -- Periodicals; 572.05
• DOI: 10.1016/j.chembiol.2016.06.010
• Languages: English
• ISSNs: 2451-9456

Abstract

Summary: 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. Graphical Abstract: Highlights: A novel highly sensitive fucose probe, 7-alkynyl-fucose, was synthesized 7-Alkynyl-fucose shows high sensitivity and low toxicity 7-Alkynyl-fucose mainly labels core fucose in glycans 7-Alkynyl-fucose can be applied to biomarker discovery, especially for cancer Abstract : Fucose sugar is often upregulated in cancer. Kizuka et al. developed a new probe for the detection of fucose. The probe shows higher sensitivity and lower toxicity than existing probes and can be applied to biomarker discovery.