Azasugar inhibitors as pharmacological chaperones for Krabbe disease† †Electronic supplementary information (ESI) available: Details of IGF, AGF, IGL and DIL syntheses including NMR spectra. Table containing X-ray data collection and refinement statistics. Dose dependence of thermal stabilization of GALC. Controls for DSF assays. IGF- and AGF-mediated stabilization of GALC is buffer and pH dependent. See DOI: 10.1039/c5sc00754b Click here for additional data file. ‡ ‡Data deposition: the atomic coordinates and structure factors have been deposited in the Protein Data Bank, http://www.pdb.org [PDB ID codes 4UFH (IGF), 4UFI (AGF), 4UFJ (IGL), 4UFK (DIL), 4UFL (DGN) and 4UFM (DGJ)].
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چکیده
Content General methods .............................................................................................................................................. S1 Apparatus ......................................................................................................................................................... S2 Abbreviations.................................................................................................................................................... S2 Synthesis ........................................................................................................................................................... S2 NMR spectra ................................................................................................................................................... S18 Small-molecule inhibition kinetics .................................................................................................................. S49 Supporting Table S1 ........................................................................................................................................ S50 Figure S1-S5 .................................................................................................................................................... S51 References ...................................................................................................................................................... S56
منابع مشابه
First synthetic analogues of diphosphoinositol polyphosphates: interaction with PP-InsP5 kinase† †Electronic supplementary information (ESI) available: Data deposition: the atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID code 4GB4). See DOI: 10.1039/c2cc36044f Click here for additional data file.
We synthesised analogues of diphosphoinositol polyphosphates (PP-InsPs) in which the diphosphate is replaced by an α-phosphonoacetic acid (PA) ester. Structural analysis revealed that 5-PA-InsP(5) mimics 5-PP-InsP(5) binding to the kinase domain of PPIP5K2; both molecules were phosphorylated by the enzyme. PA-InsPs are promising candidates for further studies into the biology of PP-InsPs.
متن کاملSynthetic tools for studying the chemical biology of InsP8 † †Electronic supplementary information (ESI) available: Data deposition: atomic coordinates and structure factors have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 5BYA and 5BYB). See DOI: 10.1039/c5cc05017k
a Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK. b Inositol Signaling Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. c Department of Pharmacology, University of Oxford, Mansfield Ro...
متن کاملProtein structure refinement using a quantum mechanics-based chemical shielding predictor† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04344e Click here for additional data file.
Additional supplementary material, including the structures used in the chemical shift prediction, can be found on Table S1. UniProt codes, names, PDB IDs and resolution of the X-ray structures, residues included in the models, and the BMRB codes of the chemical shift data of the 17 proteins used in this study. " a " indicates an NMR refined x-ray structure.
متن کاملA strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N 6-methyladenosine demethylase FTO† †Electronic supplementary information (ESI) available: Experimental details, including full synthesis procedure, T m shift analyses, biochemical and cell-based assay conditions, protein purification methods, crystallisation and structure solution methods. The coordinates and structural factors for FTO in complex with 12, 16 and 21 have been deposited in the RCSB Protein Data Bank as PDB ID 4CXW, 4CXX and 4CXY. See DOI: 10.1039/c4sc02554g Click here for additional data file.
Department of Pharmacy, National Unive 117543, Singapore. E-mail: esther.woon@n 6516 2932 Institute of Molecular and Cell Biology, 61 B School of Biological Sciences, Nanyang Tec 637551, Singapore. E-mail: [email protected] † Electronic supplementary information including full synthesis procedure, T cell-based assay conditions, protein pur structure solution methods. The coordin complex with 12, 1...
متن کاملAzasugar inhibitors as pharmacological chaperones for Krabbe disease.
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lip...
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