Aglycon specificity profiling of alpha-glucosidases using synthetic probes.
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.
Hakamata
Wataru
W
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
Muroi
Makoto
M
Kadokura
Kazunari
K
Nishio
Toshiyuki
T
Oku
Tadatake
T
Kimura
Atsuo
A
Chiba
Seiya
S
Takatsuki
Akira
A
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
D065089:Glycoside Hydrolase Inhibitors; D006539:Heptoses; C501633:deoxynojirimycine; D017485:1-Deoxynojirimycin; D005944:Glucosamine