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

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.