Abstract
Transforming a linear pentapeptidic pan-SIRT1/2/3 inhibitor harboring the catalytic mechanism-based sirtuin inhibitory warhead N(ε)-thioacetyl-lysine into its side chain-to-side chain cyclized derivatives was able to furnish highly potent SIRT1/2/3 inhibition (low nM). This finding attests to the feasibility of developing structurally simple yet highly potent catalytic mechanism-based cyclic peptidic sirtuin inhibitors.
Keywords:
Catalytic mechanism-based; Cyclic peptide; Inhibitor; Sirtuin.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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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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Humans
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Lysine / analogs & derivatives*
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Lysine / chemistry
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Lysine / pharmacology
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Models, Molecular
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Molecular Structure
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Sirtuins / antagonists & inhibitors*
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Sirtuins / metabolism
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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N(epsilon)-thioacetyllysine
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Peptides, Cyclic
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Sirtuins
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Lysine