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

[Image: see text] Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/(t)Bu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHO(t)Bu)-OH, is a potent inhibitor (IC(50) = 390 nM) of the co...

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Autores principales: Mahindra, Amit, Millard, Christopher J., Black, Iona, Archibald, Lewis J., Schwabe, John W. R., Jamieson, Andrew G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503537/
https://www.ncbi.nlm.nih.gov/pubmed/30998366
http://dx.doi.org/10.1021/acs.orglett.9b00885
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author Mahindra, Amit
Millard, Christopher J.
Black, Iona
Archibald, Lewis J.
Schwabe, John W. R.
Jamieson, Andrew G.
author_facet Mahindra, Amit
Millard, Christopher J.
Black, Iona
Archibald, Lewis J.
Schwabe, John W. R.
Jamieson, Andrew G.
author_sort Mahindra, Amit
collection PubMed
description [Image: see text] Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/(t)Bu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHO(t)Bu)-OH, is a potent inhibitor (IC(50) = 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.
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spelling pubmed-65035372019-05-08 Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups Mahindra, Amit Millard, Christopher J. Black, Iona Archibald, Lewis J. Schwabe, John W. R. Jamieson, Andrew G. Org Lett [Image: see text] Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/(t)Bu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHO(t)Bu)-OH, is a potent inhibitor (IC(50) = 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. American Chemical Society 2019-04-18 2019-05-03 /pmc/articles/PMC6503537/ /pubmed/30998366 http://dx.doi.org/10.1021/acs.orglett.9b00885 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Mahindra, Amit
Millard, Christopher J.
Black, Iona
Archibald, Lewis J.
Schwabe, John W. R.
Jamieson, Andrew G.
Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title_full Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title_fullStr Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title_full_unstemmed Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title_short Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups
title_sort synthesis of hdac substrate peptidomimetic inhibitors using fmoc amino acids incorporating zinc-binding groups
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503537/
https://www.ncbi.nlm.nih.gov/pubmed/30998366
http://dx.doi.org/10.1021/acs.orglett.9b00885
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