Abstract
In the current study, we have identified N(ε)-thiocarbamoyl-lysine (TuAcK) as a general sirtuin inhibitory warhead which was shown to be able to confer potent sirtuin inhibition. This inhibition was also shown to be mechanism-based in that the TuAck residue was able to be processed by a sirtuin enzyme with the formation of a stalled S-alkylamidate intermediate.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Lysine / analogs & derivatives
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Lysine / chemistry
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Lysine / pharmacology*
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Molecular Structure
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Sirtuins / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Thiocarbamates / chemical synthesis
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Thiocarbamates / chemistry
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Thiocarbamates / pharmacology*
Substances
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Enzyme Inhibitors
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Thiocarbamates
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Sirtuins
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Lysine