To comprehensively compare Lys acylation yield/selectivity within a nucleosome, we quantified acetylation stoichiometries of Lys residues on H2A, H2B, H3, and H4 by LC-MS/MS. While catalyst 8 selectively acetylated H2BK120 in 94% yield (Figure ), catalyst 11 selectively acetylated H2BK108 in 76% yield (Figure ). Taken together, precise optimization of the distance parameter by tuning the position of the catalytically active site on the LANA ligand, combined with the use of the BAHA warhead, dramatically switched regioselectivity of the histone acylation catalyst from H2BK120 to H2BK108.