Since H2BK43/46 are located between histone acidic patch and nucleosomal DNA, we hypothesized that a novel bivalent ligand that simultaneously binds to both acidic patch and DNA would fulfill the above requirement by conjugating the catalyst moiety in the vicinity of H2BK43/K46 (Figure ). Furthermore, the binding affinity of the bivalent ligand would be greater than monovalent LANA-based ligands, enhancing the catalyst activity with compensating the low intrinsic reactivity of H2BK43/K46. Therefore, we designed LANA-DBM by conjugating LANA with pentaarginines acting as a DNAbinding motif (DBM) through an oligoglycine (Gly) linker (Figure ). We used pentaglycines as the linker, since the distance between the C-terminus of LANA and nucleosomal DNA was estimated to be ~16 Å, which matches with the length of pentaglycines (Figure ).