79184-08-0Relevant articles and documents
Synthesis of Cell-Permeable N-Acetylhexosamine 1-Phosphates
Capota, Emanuela,Kakde, Badrinath N.,Kohler, Jennifer J.,Tambar, Uttam K.
, p. 18257 - 18264 (2021/10/25)
We recently reported the incorporation of diazirine photo-cross-linkers onto the O-GlcNAc posttranslational modification in mammalian cells, enabling the identification of binding partners of O-GlcNAcylated proteins. Unfortunately, the syntheses of the diazirine-functionalized substrates have exhibited inconsistent yields. We report a robust and stereoselective synthesis of cell-permeable GlcNAc-1-phosphate esters based on the use of commercially available bis(diisopropylamino)chlorophosphine. We demonstrate this approach for two diazirine-containing GlcNAc analogues, and we report the cellular incorporation of these compounds into glycoconjugates to support photo-cross-linking applications.
Synthesis and biological evaluation of chemical tools for the study of Dolichol Linked Oligosaccharide Diphosphatase (DLODP)
Bosco, Micha?l,Massarweh, Ahmad,Iatmanen-Harbi, Soria,Bouhss, Ahmed,Chantret, Isabelle,Busca, Patricia,Moore, Stuart E.H.,Gravier-Pelletier, Christine
, p. 952 - 964 (2016/10/25)
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.
Rationally designed short polyisoprenol-linked PglB substrates for engineered polypeptide and protein N-glycosylation
Liu, Feng,Vijayakrishnan, Balakumar,Faridmoayer, Amirreza,Taylor, Thomas A.,Parsons, Thomas B.,Bernardes, Goncalo J.L.,Kowarik, Michael,Davis, Benjamin G.
, p. 566 - 569 (2014/02/14)
The lipid carrier specificity of the protein N-glycosylation enzyme C. jejuni PglB was tested using a logical, synthetic array of natural and unnatural C10, C20, C30, and C40 polyisoprenol sugar pyrophosphates, including those bearing repeating cis-prenyl units. Unusual, short, synthetically accessible C20 prenols (nerylnerol 1d and geranylnerol 1e) were shown to be effective lipid carriers for PglB sugar substrates. Kinetic analyses for PglB revealed clear KM-only modulation with lipid chain length, thereby implicating successful in vitro application at appropriate concentrations. This was confirmed by optimized, efficient in vitro synthesis allowing >90% of Asn-linked β-N-GlcNAc-ylated peptide and proteins. This reveals a simple, flexible biocatalytic method for glycoconjugate synthesis using PglB N-glycosylation machinery and varied chemically synthesized glycosylation donor precursors.