Structural comparison of suberanilohydroxamic acid (SAHA) and other zinc-enzyme inhibitors bound to a monomeric zinc species
Histone Deacetylase (HDAC) and similar proteins contain an active Zn–OH group and have been targets for inhibitors. Known inhibitors such as suberanilohydroxamic acid (SAHA), suberohydroxamic acid (SBHA), valproic acid, and 8-hydroxyquinoline (8-HQ) derivatives act on these enzymes by binding to the zinc center. To examine how these drugs interacted with zinc centers and to examine their structural differences, a homogeneous zinc complex was synthesized and reacted with SAHA, SBHA, valproic acid, and 8-HQ to form stable adducts, which were characterized by spectroscopy and X-ray crystallography. A comparison of their structures with known complexes and enzyme active sites bound to drugs was performed in order to understand how these drugs interact with their targets.
Polyhedron Volume 114, 16 August 2016, Pages 344-350