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Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups.

ABSTRACT: Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/^tBu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHO^tBu)-OH, is a potent inhibitor (IC₅₀ = 390 nM) of the core NuRD corepressor complex (HDAC1-MTA1-RBBP4). The Fmoc amino acids have the potential to facilitate the rapid preparation of substrate peptidomimetic inhibitor (SPI) libraries in the search for selective HDAC inhibitors.

SUBMITTER: Mahindra A

PROVIDER: S-EPMC6503537 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups.

Mahindra Amit A Millard Christopher J CJ Black Iona I Archibald Lewis J LJ Schwabe John W R JWR Jamieson Andrew G AG

Organic letters 20190418 9

Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/tBu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHOtBu)-OH, is a potent inhibitor (IC50 = 390 nM) of the core NuRD corepressor complex (HDAC1-MTA1-RBBP4). The Fmoc amino acids have the potential to facilitate the rapid preparation of substrate peptidomimetic inhibitor (SPI) libraries in the search ...[more]

PMID: 30998366

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