To probe the steric requirements for deacylation, we synthesized lysine-derived small molecule substrates and examined structure-reactivity relationships with various histone deacetylases. Rat liver, human HeLa, and human recombinant class I and II histone deacetylases (HDACs) as well as human recombinant NAD+-dependent SIRT1 (class III enzyme) were used in these studies. A benzyloxycarbonyl substituent on the α-amino ...