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Aglycone-focused randomization of 2-difluoromethylphenyl-type sialoside suicide substrates for neuraminidases

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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)

Submitter: 比能 洋

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