Design and chemoenzymatic synthesis of thiooligosaccharide inhibitors of 1,3:1,4-beta-D-glucanases.
A successful chemoenzymatic synthesis of oligosaccharides with an interglucosidic sulfur atom as inhibitors of 1,3:1,4-D-glucanases is described. The key compound 3a was synthesized from acetylated 1-thio-beta-laminaribiose 4 and the methyl 4'-O-triflyl-lactoside 5. After de-O-acylation, the tetrasaccharide 3b was used as an acceptor and glucose-1-P as a donor in a phosphorolytic elongation catalysed by cellodextrin phosphorylase from Clostridium thermocellum. The expected pentasaccharide 2a and hexasaccharide 1 were isolated in 56% and 13% yield, respectively. As expected, the thiooligosaccharides 1, 2a, and 3b were resistant to enzymatic cleavage by 1,3:1,4-beta-D-glucanase isolated from Bacillus licheniformis. Furthermore, they have been shown to act as competitive inhibitors of the hydrolysis of the chromophoric trisaccharide substrate 11 by this enzyme.
Moreau
V
V
Centre de Recherches sur les Macromolécules Végétales (CERMAV-CNRS), Grenoble, France.
Viladot
J L
JL
Samain
E
E
Planas
A
A
Driguez
H
H
D001665:Binding Sites; D002240:Carbohydrate Sequence; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D005964:Glucosyltransferases; C105024:cellodextrin phosphorylase; D006026:Glycoside Hydrolases; C028020:licheninase