Enantiomeric helicenes of (P)-A and (M)-A were synthesized. The binding of the helicenes to B- and Z-DNA was studied quantitatively by CD, equilibrium dialysis, and fluorescence spectroscopy. Enantiomeric (P)-A not only bound selectively to Z-DNA, but also effectively converted the B-DNA conformation to Z-DNA. The enantio-selectivity of the helicenes offers a new route for the rational design of inhibitors of biological functions that may depend on Z-DNA.