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Aglycone-focused randomization of 2-difluoromethylphenyl-type sialoside suicide substrates for neuraminidases
Title: | Aglycone-focused randomization of 2-difluoromethylphenyl-type sialoside suicide substrates for neuraminidases |
Authors: | Kai, Hirokazu Browse this author | Hinou, Hiroshi Browse this author →KAKEN DB | Nishimura, Shin-Ichiro Browse this author →KAKEN DB |
Keywords: | Neuraminidase | Suicide substrate | Mechanism-based inhibitor | Focused library | Aglycone |
Issue Date: | 15-Apr-2012 |
Publisher: | Elsevier |
Journal Title: | Bioorganic & Medicinal Chemistry |
Volume: | 20 |
Issue: | 8 |
Start Page: | 2739 |
End Page: | 2746 |
Publisher DOI: | 10.1016/j.bmc.2012.02.001 |
PMID: | 22410247 |
Abstract: | A selective and potent inhibitor of neuraminidases, a hydrolase that is responsible for processing sialylated glycoconjugates, is a promising drug candidate for various infective diseases. The current study demonstrates that the use of an aglycone-focused library of 2-difluoromethylphenyl α-sialosides is an effective technique to find potent and selective mechanism-based labeling reagents for neuraminidases. The focused library was constructed from a 4-azide-2-difluoromethylphenyl sialoside (2) and an alkyne-terminated compound library by a click reaction. The focused library showed different inhibition patterns for two neuraminidases, Vibrio cholerae neuraminidase (VCNA) and human neuraminidase 2 (hNeu2), and the most potent inhibitors for each neuraminidase were selected. A kinetic analysis of the selected inhibitors demonstrated that the modification of the aglycone moiety improved the KI value with little change in the t_[1/2] value of the enzyme activity relative to the basic skeleton (2). |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/49556 |
Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 比能 洋
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