Through parallel studies on peptides containing N(epsilon)-methanesulfonyl-lysine or N(epsilon)-acetyl-lysine, N(epsilon)-methanesulfonyl-lysine as a replacement for N(epsilon)-acetyl-lysine was shown i) not to compromise the binding affinity for a bromodomain, ii) to confer resistance to human HDAC8 and SIRT1 (two distinct protein deacetylases), and iii) to confer only weak inhibition against human HDAC8 and SIRT1. These results suggested N(epsilon)-methanesulfonyl-lysine as a non-hydrolyzable functional surrogate for N(epsilon)-acetyl-lysine.