DNA sequence selectivity of hairpin polyamide turn units.

A class of hairpin polyamides linked by 3,4-diaminobutyric acid, resulting in a beta-amine residue at the turn unit, showed improved binding affinities relative to their alpha-amino-gamma-turn analogs for particular sequences. We incorporated beta-amino-gamma-turns in six-ring polyamides and determined whether there are any sequence preferences under the turn unit by quantitative footprinting titrations. Although there was an energetic penalty for G.C and C.G base pairs, we found little preference for T.A over A.T at the beta-amino-gamma-turn position. Fluorine and hydroxyl substituted alpha-amino-gamma-turns were synthesized for comparison. Their binding affinities and specificities in the context of six-ring polyamides demonstrated overall diminished affinity and no additional specificity at the turn position. We anticipate that this study will be a baseline for further investigation of the turn subunit as a recognition element for the DNA minor groove.