A peptidomimetic template, consisting of a hydrophobic scaffold, a dansyl fluorophore, and an Arg-His recognition strand, was tested as a simple mimic of zinc finger 2 of the Zif268 protein. Association constants (K(A)'s) were on the order of 10(5) M(-1) for complexes formed between the mimetic and duplexes d(CGGGAATTCCCG)(2) and d(AAAAAAAAATTTTTTTTT)(2). Modest selectivity was observed for the GC-rich DNA in a 0.5M NaCl/buffer (0.1M phosphate, pH 7.0) solution. Differences in K(A)'s along with observed CD profiles suggest that the mimetic associated with the duplexes using different binding modes. The DNA duplexes had weaker interactions with the free Arg-His recognition strand, the dansyl functional group, and a scaffold that contained only glycines as the recognition strand. The scaffold most likely provides for greater van der Waal's interactions, a larger hydrophobic effect upon association, and reduces the freedom of motion of the side chains. This last effect was confirmed by molecular mechanics calculations and by the fact that the mimetic suffered a smaller loss of entropic energy upon association than the free recognition strand. These studies show that the synthetic scaffold is a promising platform in which peptides can be attached to increase their affinity and possibly selectivity for DNA targets.