In this study we derived the abiotic TFs from the DNA binding domain of Max to retain functional Max homodimers for specific DNA binding to the core E-box site. The X-ray structure of the Max/Max-DNA complex revealed six key residues within the basic region that interact with the E-box sequence: Arg16, His19, Asn20, Glu23, Arg24, and Arg27 (Figure ). We envisioned that incorporating potential nonproteinogenic amino acids at these sites might augment vital TF-DNA interactions, such as hydrogen bonds and electrostatic interactions, consequently refining DNA-binding activity toward the target E-box sequence. This expansion of the chemical and interaction space would provide novel opportunities to systematically study the impact of non-natural functionalities on the DNA-binding activity and function of abiotic TFs compared to their natural counterparts.