Open AccessHistone Deacetylase 6-Selective Inhibitors and the Influence of Capping Groups on Hydroxamate-Zinc Denticity
Author(s) -
N.J. Porter,
J.D. Osko,
Daniela Diedrich,
Thomas Kurz,
Jacob M. Hooker,
Finn K. Hansen,
D.W. Christianson
Publication year - 2018
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.8b01013
Subject(s) - chemistry , hdac6 , denticity , histone deacetylase , selectivity , stereochemistry , histone , zinc , crystal structure , biochemistry , crystallography , organic chemistry , gene , catalysis
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 2+ coordination with monodentate or bidentate geometry.