Abstract
Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP-Fuc, and the direct target of 6-Alk-Fuc is FX (encoded by TSTA3), the bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a fucosylation inhibitor and its potential use for basic and clinical science. Fucose sugar is involved in cancer and inflammation. Kizuka et al. found that a fucose alkyne strongly inhibits cellular fucosylation. The compound selectively inhibits GDP-fucose synthetase FX and can be applied to glycan-related diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 1467-1478.e5 |
| Journal | Cell Chemical Biology |
| Volume | 24 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 21-12-2017 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry
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An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3. / Kizuka, Yasuhiko; Nakano, Miyako; Yamaguchi, Yoshiki; Nakajima, Kazuki; Oka, Ritsuko; Sato, Keiko; Ren, Chien Tai; Hsu, Tsui Ling; Wong, Chi Huey; Taniguchi, Naoyuki.
In: Cell Chemical Biology, Vol. 24, No. 12, 21.12.2017, p. 1467-1478.e5.Research output: Contribution to journal › Article
TY - JOUR
T1 - An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3
AU - Kizuka, Yasuhiko
AU - Nakano, Miyako
AU - Yamaguchi, Yoshiki
AU - Nakajima, Kazuki
AU - Oka, Ritsuko
AU - Sato, Keiko
AU - Ren, Chien Tai
AU - Hsu, Tsui Ling
AU - Wong, Chi Huey
AU - Taniguchi, Naoyuki
PY - 2017/12/21
Y1 - 2017/12/21
N2 - Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP-Fuc, and the direct target of 6-Alk-Fuc is FX (encoded by TSTA3), the bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a fucosylation inhibitor and its potential use for basic and clinical science. Fucose sugar is involved in cancer and inflammation. Kizuka et al. found that a fucose alkyne strongly inhibits cellular fucosylation. The compound selectively inhibits GDP-fucose synthetase FX and can be applied to glycan-related diseases.
AB - Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP-Fuc, and the direct target of 6-Alk-Fuc is FX (encoded by TSTA3), the bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a fucosylation inhibitor and its potential use for basic and clinical science. Fucose sugar is involved in cancer and inflammation. Kizuka et al. found that a fucose alkyne strongly inhibits cellular fucosylation. The compound selectively inhibits GDP-fucose synthetase FX and can be applied to glycan-related diseases.
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U2 - 10.1016/j.chembiol.2017.08.023
DO - 10.1016/j.chembiol.2017.08.023
M3 - Article
AN - SCOPUS:85031296302
VL - 24
SP - 1467-1478.e5
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 12
ER -