We have recently found that post-translational modifications of Max can dramatically influence its DNA binding activity. Importantly, we found that the acetylation of Lys31 and Lys57 significantly reduces the DNA binding affinity of Max to the E-box, potentially due to the disruption of essential salt bridges between the ammonium residue and the phosphate diester backbone. Both residues have no direct contact with the E-box nucleotides but are proximal to the phosphate DNA backbone. Lys31 and Lys57 are located approximately 3.9-16.9 Å from the DNA phosphate backbone. Here, we hypothesized that increasing the positive charge density and extending the length of the side chains, using Arg or hArg amino acids, might contribute to the DNA binding activity of Max. In total, our design includes manipulating 10 strategic sites within Max's sequence with 12 novel residues (Figure ).