title: Aglycon specificity profiling of alpha-glucosidases using synthetic probes.
abstract: We designed and synthesized hydrogen bond based probes 1-8 with the exception of known glycosidase inhibition mechanisms, and aglycon specificity of 11 different sources of alpha-glucosidases were investigated using their probes. Probe 4 (2,6-anhydro-1-deoxy-1-[(1-oxopentyl-5-hydroxy)amino]-D-glycero-D-ido-heptitol) showed a potent inhibition of S. cerevisiae alpha-glucosidase among all alpha-glucosidases. Probe 4 was found to be a competitive inhibitor for S. cerevisiae alpha-glucosidase with Ki 0.13 mM.
authors.affiliation: Animal and Cellular Systems Laboratory, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. hakamata@nihs.go.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Hakamata
authors.forename: Makoto
authors.initials: M
authors.lastname: Muroi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kadokura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nishio
authors.forename: Tadatake
authors.initials: T
authors.lastname: Oku
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kimura
authors.forename: Seiya
authors.initials: S
authors.lastname: Chiba
authors.forename: Akira
authors.initials: A
authors.lastname: Takatsuki
mesh_terms: D017485:1-Deoxynojirimycin; D000818:Animals; D015195:Drug Design; D001411:Geobacillus stearothermophilus / Q000187:drug effects / Q000201:enzymology; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors; D006539:Heptoses / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D006539:Heptoses; C501633:deoxynojirimycine; D017485:1-Deoxynojirimycin; D005944:Glucosamine