- Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme
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The class III lysine deacylases (KDACs), also known as the sirtuins, have emerged as interesting drug targets for therapeutic intervention in a variety of diseases. To gain a deeper understanding of the processes affected by sirtuins, the development of selective small molecule modulators of individual isozymes has been a longstanding goal. Essential for the discovery of novel modulators, however, are good screening protocols and mechanistic insights with regard to the targets in question. We therefore evaluated the activities of the seven human sirtuin hydrolases against a panel of fluorogenic substrates. Both commonly used, commercially available substrates and novel chemotypes designed to address recent developments in the field of lysine post-translational modification were evaluated. Our investigations led to the discovery of two new fluorogenic ε-N-succinyllysine-containing substrates that enable highly efficient and enzyme-economical screening employing sirtuin 5 (SIRT5). Furthermore, optimized protocols for facile kinetic investigations were developed, which should be valuable for enzyme kinetic investigations. Finally, these protocols were applied to a kinetic analysis of the inhibition of SIRT5 by suramin, a potent sirtuin inhibitor previously shown by X-ray crystallography to bind the substrate pocket of the human SIRT5 KDAC enzyme.
- Madsen, Andreas S.,Olsen, Christian A.
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experimental part
p. 5582 - 5590
(2012/09/21)
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- A metalation strategy for the construction of functionalized naphthalenes: The first synthesis of guieranone A
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The first synthesis of the natural product guieranone A is described, demonstrating a one-pot procedure for the synthesis of protected-1,3,6,8- tetraoxygenated naphthalenes and a subsequent directed metalation synthesis of 2-keto naphthalenes.
- McCulloch, Malcolm W.B.,Barrow, Russell A.
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p. 7619 - 7621
(2007/10/03)
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- PROCESS FOR PRODUCING ACID ANHYDRIDE
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According to the present invention there is provided a process for producing an acid anhydride by reacting a carboxylic acid, preferably a carboxylic acid having a polymerizable group, with a sulfonyl halide compound in the presence of a tertiary amine or in the presence of a tertiary amine and an inorganic base, wherein the tertiary amine or the tertiary amine and the inorganic base are used in an amount of 0.9 to 1.2 equivalents relative to the acid generated from the sulfonyl halide compound.
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Page 10-12; 14
(2008/06/13)
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- 2-Chloro-1,3-dimethylimidazolinium chloride. 1. A powerful dehydrating equivalent to DCC
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2-Chloro-1,3-dimethylimidazolinium chloride (DMC) (3) can act as a powerful dehydrating agent, replacing DCC (1) under nearly neutral conditions. Its application to acylation and dehydration is described.
- Isobe, Toshio,Ishikawa, Tsutomu
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p. 6984 - 6988
(2007/10/03)
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- COBALT(II) CHLORIDE CATALYZED SYNTHESES OF ACID ANHYDRIDES FROM ACID CHLORIDES
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Acid anhydrides were synthesized by reacting acid chlorides with carboxylic acids in the presence of catalytic quantities of cobalt(II) chloride.
- Srivastava, Rajiv R.,Kabalka, George W.
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p. 593 - 594
(2007/10/02)
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- Structural Revision and Synthesis of LL-D253α and Related Chromanone Fungal Metabolites
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The structure of LL-D253α, a chromanone metabolite of Phoma pigmentivora has been revised by analysis of the 1H-coupled 13C NMR to 7-hydroxy-8-(2'-hydroxyethyl)-5-methoxy-2-methyl-chroman-4-one.This has been further established by the synthesis of the revised and previously proposed structures of LL-D253α.
- Chandler, I. Michael,McIntyre, C. Rupert,Simpson, Thomas J.
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p. 2271 - 2284
(2007/10/02)
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- Hydroxy protection groups
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The present invention concerns a method for preparing unprotected hydroxy compounds or acylated derivatives thereof by conversion of silyl alkyl-protected hydroxy compounds. The invention also relates to novel intermediates useful in the method and for other purposes.
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- One-pot Synthesis of Acid Anhydrides from Acids Using N,N,N',N'-Tetramethylchloroformamidinium Chloride under Mild Conditions
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N,N,N',N'-Tetramethylchloroformamidinium chloride reacted smoothly with a variety of carboxylic and phosphoric acids in the presence of a tertiary amine to give the corresponding acid anhydrides in high yields.
- Fujisawa, Tamotsu,Tajima, Kazuhisa,Sato, Toshio
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p. 3529 - 3530
(2007/10/02)
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