title: Synthesis and biological evaluation of chemical tools for the study of Dolichol Linked Oligosaccharide Diphosphatase (DLODP).
abstract: Citronellyl- and solanesyl-based dolichol linked oligosaccharide (DLO) analogs were synthesized and tested along with undecaprenyl compounds for their ability to inhibit the release of [3H]OSP from [3H]DLO by mammalian liver DLO diphosphatase activity. Solanesyl (C45) and undecaprenyl (C55) compounds were 50-500 fold more potent than their citronellyl (C10)-based counterparts, indicating that the alkyl chain length is important for activity. The relative potency of the compounds within the citronellyl series was different to that of the solanesyl series with citronellyl diphosphate being 2 and 3 fold more potent than citronellyl-PP-GlcNAc2and citronellyl-PP-GlcNAc, respectively; whereas solanesyl-PP-GlcNAc and solanesyl-PP-GlcNAc2were 4 and 8 fold more potent, respectively, than solanesyl diphosphate. Undecaprenyl-PP-GlcNAc and bacterial Lipid II were 8 fold more potent than undecaprenyl diphosphate at inhibiting the DLODP assay. Therefore, at least for the more hydrophobic compounds, diphosphodiesters are more potent inhibitors of the DLODP assay than diphosphomonoesters. These results suggest that DLO rather than dolichyl diphosphate might be a preferred substrate for the DLODP activity.
authors: Université Paris Descartes, CICB-Paris, CNRS UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006, Paris, France.
authors: Michaël
authors: M
authors: Bosco
authors: Université Paris Diderot, INSERM U1149, 16 rue Henri Huchard, 75018, Paris, France.
authors: Ahmad
authors: A
authors: Massarweh
authors: Université Paris Diderot, INSERM U1149, 16 rue Henri Huchard, 75018, Paris, France.
authors: Soria
authors: S
authors: Iatmanen-Harbi
authors: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette, France.
authors: Ahmed
authors: A
authors: Bouhss
authors: Université Paris Diderot, INSERM U1149, 16 rue Henri Huchard, 75018, Paris, France.
authors: Isabelle
authors: I
authors: Chantret
authors: Université Paris Descartes, CICB-Paris, CNRS UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006, Paris, France.
authors: Patricia
authors: P
authors: Busca
authors: Université Paris Diderot, INSERM U1149, 16 rue Henri Huchard, 75018, Paris, France.
authors: Stuart E H
authors: SE
authors: Moore
authors: Université Paris Descartes, CICB-Paris, CNRS UMR 8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints-Pères, 75006, Paris, France. Electronic address: christine.gravier-pelletier@parisdescartes.fr.
authors: Christine
authors: C
authors: Gravier-Pelletier
mesh_terms: D000818:Animals; D004288:Dolichol Phosphates; D004286:Dolichols / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000201:enzymology; D039821:Monoterpenes; D009844:Oligosaccharides / Q000737:chemistry*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011105:Polyisoprenyl Phosphate Sugars; D011106:Polyisoprenyl Phosphates; D013379:Substrate Specificity
chemical_list: D004288:Dolichol Phosphates; D004286:Dolichols; D039821:Monoterpenes; D009844:Oligosaccharides; D011105:Polyisoprenyl Phosphate Sugars; D011106:Polyisoprenyl Phosphates; C026406:dolichol pyrophosphate; C063778:solanesyl pyrophosphate; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases
keywords: Biological evaluation; CDG; Diphosphatase; Disubstituted diphosphates; Glycochemistry; Phosphosugars