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Histone Deacetylase 6-Selective Inhibitors and the Influence of Capping Groups on Hydroxamate-Zinc Denticity.

ABSTRACT: Four crystal structures are presented of histone deacetylase 6 (HDAC6) complexes with para-substituted phenylhydromaxamate inhibitors, including bulky peptoids. These structures provide insight regarding the design of capping groups that confer selectivity for binding to HDAC6, specifically with regard to interactions in a pocket formed by the L1 loop. Capping group interactions may also influence hydroxamate-Zn2+ coordination with monodentate or bidentate geometry.

SUBMITTER: Porter NJ

PROVIDER: S-EPMC6136958 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Histone Deacetylase 6-Selective Inhibitors and the Influence of Capping Groups on Hydroxamate-Zinc Denticity.

Porter Nicholas J NJ Osko Jeremy D JD Diedrich Daniela D Kurz Thomas T Hooker Jacob M JM Hansen Finn K FK Christianson David W DW

Journal of medicinal chemistry 20180817 17

Four crystal structures are presented of histone deacetylase 6 (HDAC6) complexes with para-substituted phenylhydromaxamate inhibitors, including bulky peptoids. These structures provide insight regarding the design of capping groups that confer selectivity for binding to HDAC6, specifically with regard to interactions in a pocket formed by the L1 loop. Capping group interactions may also influence hydroxamate-Zn<sup>2+</sup> coordination with monodentate or bidentate geometry. ...[more]

PMID: 30118224

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