Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

Christian Adam Olsen; Ana Montero; Luke J.  Leman; M. Reza Ghadiri

doi:10.1021/ml300162r

Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

Christian Adam Olsen, Ana Montero, Luke J. Leman, M. Reza Ghadiri

Department of Chemistry

Scripps Research Institute

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.

Original language	English
Journal	ACS Medicinal Chemistry Letters
Volume	3
Issue number	9
Pages (from-to)	749-753
ISSN	1948-5875
DOIs	https://doi.org/10.1021/ml300162r
Publication status	Published - 2012

Keywords

HDAC inhibitors
Peptides
Peptoids
Macrocycles
Apicidin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/ml300162r

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abstract = "We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.",

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AU - Ghadiri, M. Reza

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AB - We report the design, synthesis, and biological evaluation of the first macrocyclic peptoid-containing histone deacetylase (HDAC) inhibitors. The compounds selectively inhibit human class I HDAC isoforms in vitro, with no inhibition of the tubulin deacetylase activity associated with class IIb HDAC6 in cultured Jurkat cells. Compared to the natural product apicidin (1), one inhibitor (compound 10) showed equivalent potency against K-562 cells, but was more cytoselective across a panel of cancer cell lines.

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KW - Peptides

KW - Peptoids

KW - Macrocycles

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U2 - 10.1021/ml300162r

DO - 10.1021/ml300162r

M3 - Journal article

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Macrocyclic Peptoid–Peptide Hybrids as Inhibitors of Class I Histone Deacetylases

Abstract

Keywords

UN SDGs

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