title: Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases.
abstract: Nine new compounds having five- and modified six-member carbohydrate core derived from D-lyxose or D-mannose, and non-hydrolysable aglycones (benzylsulfonyl or aryl(alkyl)triazolyl) were synthesised to investigate their ability to inhibit the recombinant Drosophila melanogaster homologs of two human GH38 family enzymes: Golgi mannosidase II (dGMIIb) and lysosomal mannosidase (dLMII). Two compounds were weak selective dGMIIb inhibitors showing IC50 at mM level. Moreover, it was found that another GH38 enzyme, commercial jack bean α-mannosidase, was inhibited by triazole conjugates regardless of the carbohydrate core while the corresponding sulfones were inactive.
authors.affiliation: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, SK-845 38 Bratislava, Slovakia. Electronic address: monika.polakova@savba.sk.
authors.forename: Monika
authors.initials: M
authors.lastname: Poláková
authors.affiliation: Department of Organic Chemistry, University of Palacky, Tr.17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Horák
authors.affiliation: Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, SK-845 38 Bratislava, Slovakia.
authors.forename: Sergej
authors.initials: S
authors.lastname: Šesták
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Kalinčiakova 8, SK-832 32 Bratislava, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Holková
mesh_terms: D000818:Animals; D001665:Binding Sites; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008358:Mannose / Q000737:chemistry*; D008361:Mannosidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D008958:Models, Molecular; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D008361:Mannosidases; D008358:Mannose
keywords: GH38 family; Golgi α-mannosidase; Inhibition; Lysosomal α-mannosidase; α-Mannosidase inhibitor