title: Probing the intestinal α-glucosidase enzyme specificities of starch-digesting maltase-glucoamylase and sucrase-isomaltase: synthesis and inhibitory properties of 3'- and 5'-maltose-extended de-O-sulfonated ponkoranol.
abstract: The synthesis and glucosidase inhibitory activities of two C-3'- and C-5'-β-maltose-extended analogues of the naturally occurring sulfonium-ion inhibitor, de-O-sulfonated ponkoranol, are described. The compounds are designed to test the specificity towards four intestinal glycoside hydrolase family 31 (GH31) enzyme activities, responsible for the hydrolysis of terminal starch products and sugars into glucose, in humans. The target sulfonium-ion compounds were synthesized by means of nucleophilic attack of benzyl protected 1,4-anhydro-4-thio-D-arabinitol at the C-6 position of 6-O-trifluoromethanesulfonyl trisaccharides as alkylating agents. The alkylating agents were synthesized from D-glucose by glycosylation at C-4 or C-2 with maltosyl trichloroacetimidate. Deprotection of the coupled products by using a two-step sequence, followed by reduction afforded the final compounds. Evaluation of the target compounds for inhibition of the four glucosidase activities indicated that selective inhibition of one enzyme over the others is possible.
authors: Department of Chemistry, Simon Fraser University, Burnaby, British Colombia, V5A 1S6, Canada.
authors: Razieh
authors: R
authors: Eskandari
authors: Kyra
authors: K
authors: Jones
authors: Kongara Ravinder
authors: KR
authors: Reddy
authors: Kumarasamy
authors: K
authors: Jayakanthan
authors: Marcia
authors: M
authors: Chaudet
authors: David R
authors: DR
authors: Rose
authors: B Mario
authors: BM
authors: Pinto
mesh_terms: D002384:Catalysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology*; D008320:Maltose / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013213:Starch / Q000737:chemistry*; D013237:Stereoisomerism; D013394:Sucrase-Isomaltase Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013452:Sulfonium Compounds / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013876:Thiophenes / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000737:chemistry; D000520:alpha-Glucosidases / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D013452:Sulfonium Compounds; D013876:Thiophenes; C550268:ponkoranol; D008320:Maltose; D013213:Starch; D013394:Sucrase-Isomaltase Complex; D000520:alpha-Glucosidases