Abstract
Fooling enzymes with mock amides: Analogues of apicidin, a cyclic-tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4- or 1,5-disubstituted 1,2,3-triazole in place of a backbone amide bond to fix the bond in question in either a trans-like or a cis-like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Enzyme Inhibitors / chemistry*
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Histone Deacetylase Inhibitors*
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Histone Deacetylases / metabolism
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Peptides, Cyclic / chemistry*
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Protein Conformation
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Stereoisomerism
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Structure-Activity Relationship
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Triazoles / chemistry*
Substances
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Enzyme Inhibitors
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Histone Deacetylase Inhibitors
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Peptides, Cyclic
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Triazoles
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apicidin
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Histone Deacetylases