Influence of β ‐Alanine on Hairpin Polyamide Orientation in the DNA Minor Groove

Antiparallel polyamides containing 1 H ‐pyrrole, 1 H ‐imidazole, and 3‐hydroxy‐1 H ‐pyrrole amino acids display a preference for minor‐groove binding oriented NC with respect to the 5′‐3′ direction of the DNA helix. We find that replacement of a central Py/Py pair with a β / β pair within a ten‐ring hairpin relaxes the orientation preference and, for some DNA sequences, causes the polyamide to prefer the opposite CN orientation. Substitution of the achiral γ ‐aminobutanoic acid ( γ ) with either ( R )(or S )‐2‐(acetylamino)‐4‐aminobutanoic acid moderates the orientation preference of the 2‐ β ‐2‐hairpin.