Spacer-modified oligosaccharides with basic anchoring groups are inhibitors for endo-glycanases: porcine pancreatic alpha-amylase as model enzyme.
By coupling methyl 2,3,6-tri-O-acetyl-4-O-(5-azido-6-p-tolylsulfonyloxyhexyl)-alpha-D - glucopyranoside with 2-benzoylthioethyl 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranoside, a spacer-modified disaccharide derivative, methyl 4-O-(5-azido-9-alpha-D-glucopyranosyloxy-7-thianonyl)-alpha- D-glucopyranoside, was obtained and then enzymatically glucosylated to yield the spacer-modified tri- and tetra-saccharide methyl 4-O-(5-azido-9-alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop yranoside and methyl 4-O-(5-azido-9-alpha-maltotriosyloxy-7-thianonyl)-alpha-D-gl ucopyranoside, respectively, the extended spacer spanning the length of two (1-->4)-linked pyranosyl units. The corresponding amines methyl 4-O-(5-amino-9-alpha-D-glucopyranosyloxy-7-thianonyl)-alpha- D-glucopyranoside, methyl 4-O-(5-amino-9-alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop yranoside and methyl 4-O-(5-amino-9-alpha-maltotriosyloxy-7-thianonyl)-alpha-D-gl ucopyranoside, obtained by catalytic reduction, carry the basic functionality in a spacer position to allow ionic interaction with a catalytically active acidic group in porcine pancreatic alpha-amylase (PPA). Optimal inhibition of enzymic activity is by methyl 4-O-(5-amino-9-alpha-maltosyloxy-7-thianonyl)-alpha-D-glucop yranoside where three of the five subsites are occupied by glucosyl units and the spacer spanning the remaining subsites positions the amino group near the catalytic site.
Institut für Organische Chemie und Biochemie der Universität Freiburg, Germany.
J
J
Lehmann
M
M
Schmidt-Schuchardt
D000818:Animals; D001667:Binding, Competitive; D004187:Disaccharides / Q000138:chemical synthesis / Q000737:chemistry; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D009844:Oligosaccharides / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology*; D013237:Stereoisomerism; D013552:Swine; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D004187:Disaccharides; D005960:Glucosides; D009844:Oligosaccharides; D006026:Glycoside Hydrolases; C020668:glycanase; D000516:alpha-Amylases