Back Cover: The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11 (ChemMedChem 3/2014)

Abstract

The back cover picture shows coordination of a novel silanediol histone deacetylase (HDAC) inhibitor to a Zn 2+ atom in the active site of a human HDAC enzyme. The equilibrium between keto and hydrated forms of a structurally related trifluoromethyl-ketone-containing inhibitor is also shown. The compounds are part of an array of inhibitors, which was synthesized and profiled for their potencies against recombinant human HDACs 1À11. For further details, see the Full Paper by Christian A. Olsen et al. on p. 614 ff.

Histone Deacetylase 11 Is an ε-N-Myristoyllysine Hydrolase

“…The HDAC11 Demyristoylation Activity Is Inhibited by Hydroxamic Acid-Containing Macrocycles but Not SAHA Previously, assays employing HDAC11 have been shown to require higher enzyme loading (>100 nM) (Kitir et al, 2017;Madsen et al, 2014;Madsen and Olsen, 2012a;Maolanon et al, 2014;Villadsen et al, 2014) using Kac substrates that we now show to be very poor for this enzyme. This leaves open the possibility that previously measured activities may have arisen from minute amounts of co-purified KDACs from the expression organism.…”