- Bio-inspired nitrile hydration by peptidic ligands based on L-cysteine, L-methionine or L-penicillamine and pyridine-2,6-dicarboxylic acid
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Nitrile hydratase (NHase, EC 4.2.1.84) is a metalloenzyme which catalyses the conversion of nitriles to amides. The high efficiency and broad substrate range of NHase have led to the successful application of this enzyme as a biocatalyst in the industrial syntheses of acrylamide and nicotinamide and in the bioremediation of nitrile waste. Crystal structures of both cobalt(III)- and iron(III)-dependent NHases reveal an unusual metal binding motif made up from six sequential amino acids and comprising two amide nitrogens from the peptide backbone and three cysteine-derived sulfur ligands, each at a different oxidation state (thiolate, sulfenate and sulfinate). Based on the active site geometry revealed by these crystal structures, we have designed a series of small-molecule ligands which integrate essential features of the NHase metal binding motif into a readily accessible peptide environment. We report the synthesis of ligands based on a pyridine-2,6-dicarboxylic acid scaffold and L-cysteine, L- S-methylcysteine, L-methionine or L-penicillamine. These ligands have been combined with cobalt(III) and iron(III) and tested as catalysts for biomimetic nitrile hydration. The highest levels of activity are observed with the L-penicillamine ligand which, in combination with cobalt(III), converts acetonitrile to acetamide at 1.25 turnovers and benzonitrile to benzamide at 1.20 turnovers.
- Byrne, Cillian,Houlihan, Kate M.,Devi, Prarthana,Jensen, Paul,Rutledge, Peter J.
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p. 20751 - 20767
(2015/02/19)
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- INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS
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The present invention relates to new indole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole compounds as an active ingredient.
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Page/Page column 22
(2010/08/22)
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- GLUCOKINASE ACTIVATORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE INGREDIENT
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The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.
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Page/Page column 26
(2010/11/03)
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- INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS
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The present invention relates to new indole compounds, pharmaceutically acceptable salts or isomers thereof which are useful for the prevention or treatment of cellular necrosis and necrosis-associated diseases. The present invention also relates to a method and a composition for the prevention or treatment of cellular necrosis and necrosis-associated diseases, comprising said indole compounds as an active ingredient.
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Page/Page column 73-74
(2009/04/25)
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- GLUCOKINASE ACTIVATORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE INGREDIENT
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The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.
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Page/Page column 82-83
(2009/07/25)
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- Oxidative Deblocking of the 4-Methoxybenzyl Thioether Protecting Group: Application to the Directed Synthesis of Poly-cystinyl Peptides
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The 4-methoxybenzyl thioether protecting group is deblocked efficiently by oxidation with the homogeneous electron transfer agent tris(4-bromophenyl)ammoniumyl (2.+) leading to the disulfide in high yields.S-(4-methoxybenzyl)cysteine derivatives like 9 in this way can be transformed into the corresponding cystine derivatives like 10 in 90percent yield.Many N and carboxy protecting groups like the Boc and Z group and tert-butyl or benzyl ester functions are stable under the cleavage conditions.On the other hand the 4-methoxybenzyl thioether protecting group is totally unaffected by the conditions for oxidative deblocking of the S-trityl functions by either iodine or rhodanolysis.This opens up new opportunities for the directed synthesis of cystinyl peptides with more than one intra- or interchain disulfide bridge.Application of the new method to the synthesis of a cystine peptide with one intrachain S-S-bridge and a double-chain biscystinyl peptide is reported.
- Platen, Martin,Steckhan, Eberhard
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p. 1563 - 1576
(2007/10/02)
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- Total Synthesis of Bovine Pancreatic Ribonuclease A. Part 5. Synthesis of the Protected S-Protein (Positions 21-124) and the Protected S-Peptide (Positions 1-20)
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Starting from the protected tetraoctacontapeptide corresponding to the sequence Z(OMe)-(41-124)-OBzl of bovine pancreatic RNase, the protected S-protein Z(OMe)-(RNase 21-124)-OBzl was synthesized by six successive azide condensations of the peptide fragme
- Fujii, Nobutaka,Yajima, Haruaki
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p. 819 - 830
(2007/10/02)
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