Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
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DOI：
10.1021/acs.orglett.9b00885
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发表时间：
2019-05-03
期刊：
影响因子：
5.2
通讯作者：
Jamieson, Andrew G.
中科院分区：
文献类型：
--
作者：
Mahindra, Amit;Millard, Christopher J.;Jamieson, Andrew G.
制备具有锌结合基团的Fmoc氨基酸的合成物，并使用Fmoc/Bu-t固相肽合成（SPPS）将其掺入底物抑制剂H3 K27肽中。使用Fmoc-Asu（（NHOBu）-Bu-t）-OH制备的肽11是核心NuRD辅阻遏物复合物（HDAC 1-MTA 1-RBBP 4）的强效抑制剂（IC 50 = 390 nM）。Fmoc氨基酸具有促进在寻找选择性HDAC抑制剂中快速制备底物肽模拟物抑制剂（SPI）文库的潜力。
Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/Bu-t solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu((NHOBu)-Bu-t)-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.